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{{Infobox_gene}}
{{PBB_Controls
'''Rod cGMP-specific 3',5'-cyclic phosphodiesterase subunit beta''' is the beta subunit of the protein complex PDE6 that is encoded by the ''PDE6B'' [[gene]].<ref name="pmid1313787">{{cite journal | vauthors = Bateman JB, Klisak I, Kojis T, Mohandas T, Sparkes RS, Li TS, Applebury ML, Bowes C, Farber DB | title = Assignment of the beta-subunit of rod photoreceptor cGMP phosphodiesterase gene PDEB (homolog of the mouse rd gene) to human chromosome 4p16 | journal = Genomics | volume = 12 | issue = 3 | pages = 601–3 | date = Mar 1992 | pmid = 1313787 | pmc =  | doi = 10.1016/0888-7543(92)90454-Z }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: PDE6B phosphodiesterase 6B, cGMP-specific, rod, beta (congenital stationary night blindness 3, autosomal dominant)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5158| accessdate = }}</ref> PDE6 is crucial in transmission and amplification of visual signal. The existence of this beta subunit is essential for normal PDE6 functioning. Mutations in this subunit are responsible for retinal degeneration such as [[retinitis pigmentosa]]<ref name="pmid11559856">{{cite journal | vauthors = Wang Q, Chen Q, Zhao K, Wang L, Wang L, Traboulsi EI | title = Update on the molecular genetics of retinitis pigmentosa | journal = Ophthalmic Genetics | volume = 22 | issue = 3 | pages = 133–54 | year = 2001 | pmid = 11559856 | doi = 10.1076/opge.22.3.133.2224| url = }}</ref><ref>{{cite journal|last1=Danciger|first1=M|last2=Blaney|first2=J|last3=Gao|first3=YQ|last4=Zhao|first4=DY|last5=Heckenlively|first5=JR|last6=Jacobson|first6=SG|last7=Farber|first7=DB|title=Mutations in the PDE6B gene in autosomal recessive retinitis pigmentosa|journal=Genomics|date=1 November 1995|volume=30|issue=1|pages=1–7|pmid=8595886|doi=10.1006/geno.1995.0001}}</ref> or congenital stationary [[night blindness]].<ref>{{cite web|url=https://sph.uth.edu/Retnet/disease.htm#04.103d|website=RetNet|title=RetNet: Genes and Mapped Loci Causing Retinal Diseases|accessdate=12 May 2015}}</ref>
| update_page = yes
| require_manual_inspection = no
| update_protein_box = yes
| update_summary = yes
| update_citations = yes
}}


<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
== Structure ==
{{GNF_Protein_box
| image =
| image_source =
| PDB =  
| Name = Phosphodiesterase 6B, cGMP-specific, rod, beta (congenital stationary night blindness 3, autosomal dominant)
| HGNCid = 8786
| Symbol = PDE6B
| AltSymbols =; CSNB3; PDEB; rd1
| OMIM = 180072
| ECnumber = 
| Homologene = 237
| MGIid = 97525
| GeneAtlas_image1 = PBB_GE_PDE6B_210304_at_tn.png
| Function = {{GNF_GO|id=GO:0016787 |text = hydrolase activity}} {{GNF_GO|id=GO:0047555 |text = 3',5'-cyclic-GMP phosphodiesterase activity}}
| Component = {{GNF_GO|id=GO:0016020 |text = membrane}}
| Process = {{GNF_GO|id=GO:0007165 |text = signal transduction}} {{GNF_GO|id=GO:0007601 |text = visual perception}} {{GNF_GO|id=GO:0007603 |text = phototransduction, visible light}} {{GNF_GO|id=GO:0050896 |text = response to stimulus}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 5158
    | Hs_Ensembl = ENSG00000133256
    | Hs_RefseqProtein = NP_000274
    | Hs_RefseqmRNA = NM_000283
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 4
    | Hs_GenLoc_start = 609373
    | Hs_GenLoc_end = 653896
    | Hs_Uniprot = P35913
    | Mm_EntrezGene = 18587
    | Mm_Ensembl = ENSMUSG00000029491
    | Mm_RefseqmRNA = NM_008806
    | Mm_RefseqProtein = NP_032832
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 5
    | Mm_GenLoc_start = 108628694
    | Mm_GenLoc_end = 108672034
    | Mm_Uniprot = Q60937
  }}
}}
'''Phosphodiesterase 6B, cGMP-specific, rod, beta (congenital stationary night blindness 3, autosomal dominant)''', also known as '''PDE6B''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: PDE6B phosphodiesterase 6B, cGMP-specific, rod, beta (congenital stationary night blindness 3, autosomal dominant)| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5158| accessdate = }}</ref>


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
[[File:PDE6B.jpg|framed|left|Structure of Rod Phosphodiesterase 6 complex showing the GAF (GAF1 & GAF2) and catalytic (CAT) domains]]
{{PBB_Summary
PDE6 is a protein complex located on the [[photoreceptor cell|photoreceptor]]'s outer segment, and plays an important role in the [[phototransduction]] cascade.<ref>{{cite journal | vauthors = Han J, Dinculescu A, Dai X, Du W, Smith WC, Pang J | title = Review: the history and role of naturally occurring mouse models with Pde6b mutations | journal = Molecular Vision | volume = 19 | pages = 2579–89 | date = 20 December 2013 | pmid = 24367157 | pmc=3869645}}</ref> There are two types of photoreceptors: [[cone cell|cone]]s and [[rod cell|rod]]s. The rod and cone PDE6 complexes have different structures. PDE6β together with [[PDE6A|PDE6α]] and two identical inhibitory subunits, [[PDE6G|PDE6γ]], form the rod PDE6 [[holoenzyme]] while the cone PDE6 complex only consists of two identical PDE6α' catalytic subunits.<ref name="pmid15224133">{{cite journal | vauthors = Cote RH | title = Characteristics of photoreceptor PDE (PDE6): similarities and differences to PDE5 | journal = International Journal of Impotence Research | volume = 16 Suppl 1 | pages = S28-33 | date = Jun 2004 | pmid = 15224133 | doi = 10.1038/sj.ijir.3901212 }}</ref> PDE6β, one of the catalytic units in rod PDE6, is composed of three domains: two [[N-terminal]] [[GAF domain]]s and one [[C-terminal]] catalytic domain.The non-catalytic GAF domains are responsible for [[Cyclic guanosine monophosphate|cGMP]] binding. The C-terminal interacts with cell membrane by [[isoprenylation]] and S-carboxylmethylation.<ref name="pmid15224133" />
| section_title =
| summary_text = Mice homozygous for the rd mutation display hereditary retinal degeneration which has been considered a model for human retinitis pigmentosa. In affected animals, the retinal rod photoreceptor cells begin degenerating at about postnatal day 8, and by 4 weeks no photoreceptors are left. Farber and Lolley (1974, 1976) showed that degeneration is preceded by accumulation of cyclic GMP in the retina and is correlated with deficient activity of the rod photoreceptor cGMP-phosphodiesterase. Bennett et al. (1996) tested the possibility of altering the course of retinal degeneration through subretinal injection of recombinant replication defective adenovirus that contained the murine cDNA for wildtype beta-PDE. Subretinal injection of rd mice was carried out 4 days after birth, before the onset of rd retinal degeneration. Following therapy, beta-PDE transcripts and enzyme activity were detected, and histologic studies revealed that photoreceptor cell death was significantly retarded.[supplied by OMIM]<ref name="entrez">{{cite web | title = Entrez Gene: PDE6B phosphodiesterase 6B, cGMP-specific, rod, beta (congenital stationary night blindness 3, autosomal dominant)| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5158| accessdate = }}</ref>
}}


==References==
== Function ==
{{reflist|2}}
 
==Further reading==
Absorption of photons by [[rhodopsin]] triggers a [[signal transduction]] cascade in rod photoreceptors. This [[phototransduction]] cascade leads to hydrolysis of [[Cyclic guanosine monophosphate|cGMP]] by cGMP-[[phosphodiesterase]] (PDE) that closes [[cyclic nucleotide-gated ion channel|cGMP-gated channels]] and hyperpolarizes the cell.<ref name = "Khramtsov_1993">{{cite journal | vauthors = Khramtsov NV, Feshchenko EA, Suslova VA, Shmukler BE, Terpugov BE, Rakitina TV, Atabekova NV, Lipkin VM | title = The human rod photoreceptor cGMP phosphodiesterase beta-subunit. Structural studies of its cDNA and gene | journal = FEBS Letters | volume = 327 | issue = 3 | pages = 275–8 | date = Aug 1993 | pmid = 8394243 | doi = 10.1016/0014-5793(93)81003-I }}</ref> PDE6β is necessary for the formation of a functional phosphodiesterase holoenzyme.<ref name="pmid15224133"/>
{{refbegin | 2}}
 
{{PBB_Further_reading
=== Function of PDE6 ===
| citations =  
 
*{{cite journal | author=Lerner LE, Piri N, Farber DB |title=Transcriptional and post-transcriptional regulation of the rod cGMP-phosphodiesterase beta-subunit gene. Recent advances and current concepts. |journal=Adv. Exp. Med. Biol. |volume=572 |issue= |pages= 217-29 |year= 2007 |pmid= 17249578 |doi= }}
PDE6 is a highly concentrated protein in retinal photoreceptors. With the presence of the GAF domain, PDE6 can actively bind to the cGMP. The inactive PDE6 in the dark allows cGMP to bind to [[Cyclic nucleotide-gated ion channel|cGMP gated ion channels]]. The channel remains open as long as cGMP is binding to it, which allows constant electron flow in to the photoreceptor cell through the [[plasma membrane]]. Light causes the visual pigment, [[rhodopsin]], to activate. This process leads to the release of subunit PDE6γ from PDE6αβ, activating PDE6 which leads to the [[hydrolysis]] of cGMP. Without the cGMP binding, the ion channel closes, leading to the [[Hyperpolarization (biology)|hyperpolarization]].<ref name="pmid15224133"/> After hyperpolarization the presnaptic transimitter is reduced. Next, the enzyme [[guanylate cyclase]] restores cGMP, which reopens the membrane channels. This process is called light adaptation.
*{{cite journal  | author=Farber DB, Lolley RN |title=Enzymic basis for cyclic GMP accumulation in degenerative photoreceptor cells of mouse retina. |journal=Journal of cyclic nucleotide research |volume=2 |issue= 3 |pages= 139-48 |year= 1976 |pmid= 6493 |doi=  }}
 
*{{cite journal  | author=Bateman JB, Klisak I, Kojis T, ''et al.'' |title=Assignment of the beta-subunit of rod photoreceptor cGMP phosphodiesterase gene PDEB (homolog of the mouse rd gene) to human chromosome 4p16. |journal=Genomics |volume=12 |issue= 3 |pages= 601-3 |year= 1992 |pmid= 1313787 |doi= }}
=== Function of PDE6B ===
*{{cite journal  | author=Altherr MR, Wasmuth JJ, Seldin MF, ''et al.'' |title=Chromosome mapping of the rod photoreceptor cGMP phosphodiesterase beta-subunit gene in mouse and human: tight linkage to the Huntington disease region (4p16.3). |journal=Genomics |volume=12 |issue= 4 |pages= 750-4 |year= 1992 |pmid= 1315306 |doi= }}
 
*{{cite journal  | author=Collins C, Hutchinson G, Kowbel D, ''et al.'' |title=The human beta-subunit of rod photoreceptor cGMP phosphodiesterase: complete retinal cDNA sequence and evidence for expression in brain. |journal=Genomics |volume=13 |issue= 3 |pages= 698-704 |year= 1992 |pmid= 1322354 |doi=  }}
PDE6β is the only protein that undergoes the two types of [[post-translational modification]], [[prenylation]] and [[carboxymethylation]].<ref>{{cite journal | vauthors = Anant JS, Ong OC, Xie HY, Clarke S, O'Brien PJ, Fung BK | title = In vivo differential prenylation of retinal cyclic GMP phosphodiesterase catalytic subunits | journal = The Journal of Biological Chemistry | volume = 267 | issue = 2 | pages = 687–90 | date = Jan 1992 | pmid = 1309771 }}</ref> The [[geranylgeranyl group]] of PDE6B is the result of these modifications, which are responsible for the rod PDE6's interaction with membrane.
*{{cite journal | author=Catty P, Pfister C, Bruckert F, Deterre P |title=The cGMP phosphodiesterase-transducin complex of retinal rods. Membrane binding and subunits interactions. |journal=J. Biol. Chem. |volume=267 |issue= 27 |pages= 19489-93 |year= 1992 |pmid= 1326553 |doi= }}
 
*{{cite journal  | author=Khramtsov NV, Feshchenko EA, Suslova VA, ''et al.'' |title=[Structural studies of cDNA and the gene for the beta-subunit of cGMP phosphodiesterase from human retina] |journal=Bioorg. Khim. |volume=18 |issue= 12 |pages= 1551-4 |year= 1993 |pmid= 1338685 |doi= }}
== Animal studies ==
*{{cite journal  | author=Weber B, Riess O, Hutchinson G, ''et al.'' |title=Genomic organization and complete sequence of the human gene encoding the beta-subunit of the cGMP phosphodiesterase and its localisation to 4p 16.3. |journal=Nucleic Acids Res. |volume=19 |issue= 22 |pages= 6263-8 |year= 1991 |pmid= 1720239 |doi= }}
 
*{{cite journal  | author=Farber DB, Lolley RN |title=Cyclic guanosine monophosphate: elevation in degenerating photoreceptor cells of the C3H mouse retina. |journal=Science |volume=186 |issue= 4162 |pages= 449-51 |year= 1974 |pmid= 4369896 |doi= }}
===''rd1'' mouse===
*{{cite journal  | author=McLaughlin ME, Ehrhart TL, Berson EL, Dryja TP |title=Mutation spectrum of the gene encoding the beta subunit of rod phosphodiesterase among patients with autosomal recessive retinitis pigmentosa. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=92 |issue= 8 |pages= 3249-53 |year= 1995 |pmid= 7724547 |doi=  }}
Mutation of the ''PDE6b'' gene leads to the dysfunction of PDE, which results in failure of hydrolysis of cGMP. The ''rd1'' mouse is a well-characterized animal model of retinitis pigmentosa caused by the mutation of Pde6b gene.<ref name="ReferenceA">{{cite journal | vauthors = Farber DB, Lolley RN | title = Enzymic basis for cyclic GMP accumulation in degenerative photoreceptor cells of mouse retina | journal = Journal of Cyclic Nucleotide Research | volume = 2 | issue = 3 | pages = 139–48 | year = 1976 | pmid = 6493 | doi =  }}</ref> The phenotype was first discovered in rodless mice in the 1920s by Keeler.<ref>{{cite journal|last1=Keeler|first1=CE|title=The Geotropic Reaction of Rodless Mice in LIght and in Darkness|journal=The Journal of General Physiology|date=20 March 1928|volume=11|issue=4|pages=361–8|pmid=19872404|doi=10.1085/jgp.11.4.361|pmc=2140980}}</ref> An insertion of Murine leukemia [[provirus]] is present near the first [[exon]] combined with a point mutation, which introduces a stop codon in exon 7. In addition to the ''rd1'' mouse, a missense mutation (R560C) in exon 13 of the ''Pde6b'' gene is the character of another animal model of recessive retinal degeneration.
*{{cite journal  | author=Gal A, Orth U, Baehr W, ''et al.'' |title=Heterozygous missense mutation in the rod cGMP phosphodiesterase beta-subunit gene in autosomal dominant stationary night blindness. |journal=Nat. Genet. |volume=7 |issue= 4 |pages= 551 |year= 1994 |pmid= 7951329 |doi= 10.1038/ng0894-551a }}
 
*{{cite journal  | author=Gal A, Orth U, Baehr W, ''et al.'' |title=Heterozygous missense mutation in the rod cGMP phosphodiesterase beta-subunit gene in autosomal dominant stationary night blindness. |journal=Nat. Genet. |volume=7 |issue= 1 |pages= 64-8 |year= 1994 |pmid= 8075643 |doi= 10.1038/ng0594-64 }}
In ''rd1'' animals, the retinal rod photoreceptor cells begin degenerating at about postnatal day 10, and by 3 weeks no rod photoreceptors remain. Degeneration is preceded by accumulation of cGMP in the retina and is correlated with deficient activity of the rod photoreceptor cGMP-phosphodiesterase.<ref name="ReferenceA"/><ref>{{cite journal | vauthors = Farber DB, Lolley RN | title = Cyclic guanosine monophosphate: elevation in degenerating photoreceptor cells of the C3H mouse retina | journal = Science | volume = 186 | issue = 4162 | pages = 449–51 | date = Nov 1974 | pmid = 4369896 | doi = 10.1126/science.186.4162.449 }}</ref> Cone photoreceptors undergo a slower degeneration over the course of a year, which causes the mutants to completely go blind.<ref>{{cite journal | vauthors = Chang B, Hawes NL, Hurd RE, Davisson MT, Nusinowitz S, Heckenlively JR | title = Retinal degeneration mutants in the mouse | journal = Vision Research | volume = 42 | issue = 4 | pages = 517–25 | date = Feb 2002 | pmid = 11853768 | doi=10.1016/s0042-6989(01)00146-8}}</ref> The possibility of altering the course of retinal degeneration through subretinal injection of recombinant replication defective [[adenovirus]] that contained the murine cDNA for wildtype PDE6β was tested in ''rd1'' mice.<ref>{{cite journal | vauthors = Bennett J, Tanabe T, Sun D, Zeng Y, Kjeldbye H, Gouras P, Maguire AM | title = Photoreceptor cell rescue in retinal degeneration (rd) mice by in vivo gene therapy | journal = Nature Medicine | volume = 2 | issue = 6 | pages = 649–54 | date = Jun 1996 | pmid = 8640555 | doi = 10.1038/nm0696-649 }}</ref> Subretinal injection of ''rd1'' mice was carried out 4 days after birth, before the onset of rod photoreceptor degeneration. Following therapy, Pde6β transcripts and enzyme activity were detected, and histologic studies revealed that photoreceptor cell death was significantly retarded.<ref name="entrez"/>
*{{cite journal  | author=McLaughlin ME, Sandberg MA, Berson EL, Dryja TP |title=Recessive mutations in the gene encoding the beta-subunit of rod phosphodiesterase in patients with retinitis pigmentosa. |journal=Nat. Genet. |volume=4 |issue= 2 |pages= 130-4 |year= 1993 |pmid= 8394174 |doi= 10.1038/ng0693-130 }}
 
*{{cite journal | author=Khramtsov NV, Feshchenko EA, Suslova VA, ''et al.'' |title=The human rod photoreceptor cGMP phosphodiesterase beta-subunit. Structural studies of its cDNA and gene. |journal=FEBS Lett. |volume=327 |issue= 3 |pages= 275-8 |year= 1993 |pmid= 8394243 |doi= }}
The albino [[FVB mouse]] laboratory strain become blind by weaning age due to a mutant allele of the ''PDE6b'' gene. There are pigmented derivative strains of FVB that lack this trait.
*{{cite journal | author=Valverde D, Solans T, Grinberg D, ''et al.'' |title=A novel mutation in exon 17 of the beta-subunit of rod phosphodiesterase in two RP sisters of a consanguineous family. |journal=Hum. Genet. |volume=97 |issue= 1 |pages= 35-8 |year= 1996 |pmid= 8557257 |doi=  }}
 
*{{cite journal | author=Danciger M, Blaney J, Gao YQ, ''et al.'' |title=Mutations in the PDE6B gene in autosomal recessive retinitis pigmentosa. |journal=Genomics |volume=30 |issue= 1 |pages= 1-7 |year= 1996 |pmid= 8595886 |doi= 10.1006/geno.1995.0001 }}
===''rcd1'' dog===
*{{cite journal | author=Bennett J, Tanabe T, Sun D, ''et al.'' |title=Photoreceptor cell rescue in retinal degeneration (rd) mice by in vivo gene therapy. |journal=Nat. Med. |volume=2 |issue= 6 |pages= 649-54 |year= 1996 |pmid= 8640555 |doi= }}
 
*{{cite journal | author=Gao YQ, Danciger M, Zhao DY, ''et al.'' |title=Screening of the PDE6B gene in patients with autosomal dominant retinitis pigmentosa. |journal=Exp. Eye Res. |volume=62 |issue= 2 |pages= 149-54 |year= 1996 |pmid= 8698075 |doi= 10.1006/exer.1996.0019 }}
Similar to ''rd1'' in mice, Rod-cone dysplasia type 1 (rcd1-PRA) is a form of [[progressive retinal atrophy]] (PRA), with early onset of the disease. The [[Irish Setter]] is a characterized animal model of rcd1. The mutation is caused by a nonsense mutation in ''pde6b'' gene. Photoreceptors start degeneration at postnatal day 13 until a year after the dog is totally blind.<ref>{{cite journal | vauthors = Petit L, Lhériteau E, Weber M, Le Meur G, Deschamps JY, Provost N, Mendes-Madeira A, Libeau L, Guihal C, Colle MA, Moullier P, Rolling F | title = Restoration of vision in the pde6β-deficient dog, a large animal model of rod-cone dystrophy | journal = Molecular Therapy | volume = 20 | issue = 11 | pages = 2019–30 | date = Nov 2012 | pmid = 22828504 | doi = 10.1038/mt.2012.134 | pmc=3498794}}</ref>
*{{cite journal | author=Suslova VA, Suslov ON, Kim EE, Lipkin VM |title=[Organization of the gene for the beta-subunit of human photoreceptor cyclic GMP phosphodiesterase] |journal=Bioorg. Khim. |volume=22 |issue= 4 |pages= 256-63 |year= 1996 |pmid= 8768262 |doi= }}
 
*{{cite journal | author=Valverde D, Baiget M, Seminago R, ''et al.'' |title=Identification of a novel R552O mutation in exon 13 of the beta-subunit of rod phosphodiesterase gene in a Spanish family with autosomal recessive retinitis pigmentosa. |journal=Hum. Mutat. |volume=8 |issue= 4 |pages= 393-4 |year= 1997 |pmid= 8956055 |doi= 10.1002/humu.1380080403 }}
== References ==
}}
{{reflist|33em}}
 
== Further reading ==
{{refbegin|33em}}
* {{cite journal | vauthors = Lerner LE, Piri N, Farber DB | title = Transcriptional and post-transcriptional regulation of the rod cGMP-phosphodiesterase beta-subunit gene. Recent advances and current concepts | journal = Advances in Experimental Medicine and Biology | volume = 572 | issue =  | pages = 217–29 | year = 2007 | pmid = 17249578 | doi = 10.1007/0-387-32442-9_32 | isbn = 978-0-387-28464-4 | series = Advances in Experimental Medicine and Biology }}
* {{cite journal | vauthors = Altherr MR, Wasmuth JJ, Seldin MF, Nadeau JH, Baehr W, Pittler SJ | title = Chromosome mapping of the rod photoreceptor cGMP phosphodiesterase beta-subunit gene in mouse and human: tight linkage to the Huntington disease region (4p16.3) | journal = Genomics | volume = 12 | issue = 4 | pages = 750–4 | date = Apr 1992 | pmid = 1315306 | doi = 10.1016/0888-7543(92)90305-C }}
* {{cite journal | vauthors = Collins C, Hutchinson G, Kowbel D, Riess O, Weber B, Hayden MR | title = The human beta-subunit of rod photoreceptor cGMP phosphodiesterase: complete retinal cDNA sequence and evidence for expression in brain | journal = Genomics | volume = 13 | issue = 3 | pages = 698–704 | date = Jul 1992 | pmid = 1322354 | doi = 10.1016/0888-7543(92)90144-H }}
* {{cite journal | vauthors = Catty P, Pfister C, Bruckert F, Deterre P | title = The cGMP phosphodiesterase-transducin complex of retinal rods. Membrane binding and subunits interactions | journal = The Journal of Biological Chemistry | volume = 267 | issue = 27 | pages = 19489–93 | date = Sep 1992 | pmid = 1326553 | doi =  }}
* {{cite journal | vauthors = Khramtsov NV, Feshchenko EA, Suslova VA, Terpugov BE, Rakitina TV, Atabekova NV, Shmukler BE, Lipkin VM | title = [Structural studies of cDNA and the gene for the beta-subunit of cGMP phosphodiesterase from human retina] | journal = Bioorganicheskaia Khimiia | volume = 18 | issue = 12 | pages = 1551–4 | date = Dec 1992 | pmid = 1338685 | doi = }}
* {{cite journal | vauthors = Weber B, Riess O, Hutchinson G, Collins C, Lin BY, Kowbel D, Andrew S, Schappert K, Hayden MR | title = Genomic organization and complete sequence of the human gene encoding the beta-subunit of the cGMP phosphodiesterase and its localisation to 4p 16.3 | journal = Nucleic Acids Research | volume = 19 | issue = 22 | pages = 6263–8 | date = Nov 1991 | pmid = 1720239 | pmc = 329137 | doi = 10.1093/nar/19.22.6263 }}
* {{cite journal | vauthors = McLaughlin ME, Ehrhart TL, Berson EL, Dryja TP | title = Mutation spectrum of the gene encoding the beta subunit of rod phosphodiesterase among patients with autosomal recessive retinitis pigmentosa | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 92 | issue = 8 | pages = 3249–53 | date = Apr 1995 | pmid = 7724547 | pmc = 42143 | doi = 10.1073/pnas.92.8.3249 }}
* {{cite journal | vauthors = Gal A, Orth U, Baehr W, Schwinger E, Rosenberg T | title = Heterozygous missense mutation in the rod cGMP phosphodiesterase beta-subunit gene in autosomal dominant stationary night blindness | journal = Nature Genetics | volume = 7 | issue = 4 | pages = 551 | date = Aug 1994 | pmid = 7951329 | doi = 10.1038/ng0894-551a }}
* {{cite journal | vauthors = Gal A, Orth U, Baehr W, Schwinger E, Rosenberg T | title = Heterozygous missense mutation in the rod cGMP phosphodiesterase beta-subunit gene in autosomal dominant stationary night blindness | journal = Nature Genetics | volume = 7 | issue = 1 | pages = 64–8 | date = May 1994 | pmid = 8075643 | doi = 10.1038/ng0594-64 }}
* {{cite journal | vauthors = McLaughlin ME, Sandberg MA, Berson EL, Dryja TP | title = Recessive mutations in the gene encoding the beta-subunit of rod phosphodiesterase in patients with retinitis pigmentosa | journal = Nature Genetics | volume = 4 | issue = 2 | pages = 130–4 | date = Jun 1993 | pmid = 8394174 | doi = 10.1038/ng0693-130 }}
* {{cite journal | vauthors = Valverde D, Solans T, Grinberg D, Balcells S, Vilageliu L, Bayés M, Chivelet P, Besmond C, Goossens M, González-Duarte R, Baiget M | title = A novel mutation in exon 17 of the beta-subunit of rod phosphodiesterase in two RP sisters of a consanguineous family | journal = Human Genetics | volume = 97 | issue = 1 | pages = 35–8 | date = Jan 1996 | pmid = 8557257 | doi = 10.1007/BF00218829 }}
* {{cite journal | vauthors = Gao YQ, Danciger M, Zhao DY, Blaney J, Piriev NI, Shih J, Jacobson SG, Heckenlively JH, Farber DB | title = Screening of the PDE6B gene in patients with autosomal dominant retinitis pigmentosa | journal = Experimental Eye Research | volume = 62 | issue = 2 | pages = 149–54 | date = Feb 1996 | pmid = 8698075 | doi = 10.1006/exer.1996.0019 }}
* {{cite journal | vauthors = Suslova VA, Suslov ON, Kim EE, Lipkin VM | title = [Organization of the gene for the beta-subunit of human photoreceptor cyclic GMP phosphodiesterase] | journal = Bioorganicheskaia Khimiia | volume = 22 | issue = 4 | pages = 256–63 | date = Apr 1996 | pmid = 8768262 | doi =  }}
* {{cite journal | vauthors = Valverde D, Baiget M, Seminago R, del Rio E, García-Sandoval B, del Rio T, Bayés M, Balcells S, Martínez A, Grinberg D, Ayuso C | title = Identification of a novel R552O mutation in exon 13 of the beta-subunit of rod phosphodiesterase gene in a Spanish family with autosomal recessive retinitis pigmentosa | journal = Human Mutation | volume = 8 | issue = 4 | pages = 393–4 | year = 1997 | pmid = 8956055 | doi = 10.1002/humu.1380080403 }}
{{refend}}
{{refend}}


{{protein-stub}}
== External links ==
{{WikiDoc Sources}}
* [https://www.ncbi.nlm.nih.gov/books/NBK1417/  GeneReviews/NCBI/NIH/UW entry on Retinitis Pigmentosa Overview]

Revision as of 14:30, 24 November 2017

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Rod cGMP-specific 3',5'-cyclic phosphodiesterase subunit beta is the beta subunit of the protein complex PDE6 that is encoded by the PDE6B gene.[1][2] PDE6 is crucial in transmission and amplification of visual signal. The existence of this beta subunit is essential for normal PDE6 functioning. Mutations in this subunit are responsible for retinal degeneration such as retinitis pigmentosa[3][4] or congenital stationary night blindness.[5]

Structure

File:PDE6B.jpg
Structure of Rod Phosphodiesterase 6 complex showing the GAF (GAF1 & GAF2) and catalytic (CAT) domains

PDE6 is a protein complex located on the photoreceptor's outer segment, and plays an important role in the phototransduction cascade.[6] There are two types of photoreceptors: cones and rods. The rod and cone PDE6 complexes have different structures. PDE6β together with PDE6α and two identical inhibitory subunits, PDE6γ, form the rod PDE6 holoenzyme while the cone PDE6 complex only consists of two identical PDE6α' catalytic subunits.[7] PDE6β, one of the catalytic units in rod PDE6, is composed of three domains: two N-terminal GAF domains and one C-terminal catalytic domain.The non-catalytic GAF domains are responsible for cGMP binding. The C-terminal interacts with cell membrane by isoprenylation and S-carboxylmethylation.[7]

Function

Absorption of photons by rhodopsin triggers a signal transduction cascade in rod photoreceptors. This phototransduction cascade leads to hydrolysis of cGMP by cGMP-phosphodiesterase (PDE) that closes cGMP-gated channels and hyperpolarizes the cell.[8] PDE6β is necessary for the formation of a functional phosphodiesterase holoenzyme.[7]

Function of PDE6

PDE6 is a highly concentrated protein in retinal photoreceptors. With the presence of the GAF domain, PDE6 can actively bind to the cGMP. The inactive PDE6 in the dark allows cGMP to bind to cGMP gated ion channels. The channel remains open as long as cGMP is binding to it, which allows constant electron flow in to the photoreceptor cell through the plasma membrane. Light causes the visual pigment, rhodopsin, to activate. This process leads to the release of subunit PDE6γ from PDE6αβ, activating PDE6 which leads to the hydrolysis of cGMP. Without the cGMP binding, the ion channel closes, leading to the hyperpolarization.[7] After hyperpolarization the presnaptic transimitter is reduced. Next, the enzyme guanylate cyclase restores cGMP, which reopens the membrane channels. This process is called light adaptation.

Function of PDE6B

PDE6β is the only protein that undergoes the two types of post-translational modification, prenylation and carboxymethylation.[9] The geranylgeranyl group of PDE6B is the result of these modifications, which are responsible for the rod PDE6's interaction with membrane.

Animal studies

rd1 mouse

Mutation of the PDE6b gene leads to the dysfunction of PDE, which results in failure of hydrolysis of cGMP. The rd1 mouse is a well-characterized animal model of retinitis pigmentosa caused by the mutation of Pde6b gene.[10] The phenotype was first discovered in rodless mice in the 1920s by Keeler.[11] An insertion of Murine leukemia provirus is present near the first exon combined with a point mutation, which introduces a stop codon in exon 7. In addition to the rd1 mouse, a missense mutation (R560C) in exon 13 of the Pde6b gene is the character of another animal model of recessive retinal degeneration.

In rd1 animals, the retinal rod photoreceptor cells begin degenerating at about postnatal day 10, and by 3 weeks no rod photoreceptors remain. Degeneration is preceded by accumulation of cGMP in the retina and is correlated with deficient activity of the rod photoreceptor cGMP-phosphodiesterase.[10][12] Cone photoreceptors undergo a slower degeneration over the course of a year, which causes the mutants to completely go blind.[13] The possibility of altering the course of retinal degeneration through subretinal injection of recombinant replication defective adenovirus that contained the murine cDNA for wildtype PDE6β was tested in rd1 mice.[14] Subretinal injection of rd1 mice was carried out 4 days after birth, before the onset of rod photoreceptor degeneration. Following therapy, Pde6β transcripts and enzyme activity were detected, and histologic studies revealed that photoreceptor cell death was significantly retarded.[2]

The albino FVB mouse laboratory strain become blind by weaning age due to a mutant allele of the PDE6b gene. There are pigmented derivative strains of FVB that lack this trait.

rcd1 dog

Similar to rd1 in mice, Rod-cone dysplasia type 1 (rcd1-PRA) is a form of progressive retinal atrophy (PRA), with early onset of the disease. The Irish Setter is a characterized animal model of rcd1. The mutation is caused by a nonsense mutation in pde6b gene. Photoreceptors start degeneration at postnatal day 13 until a year after the dog is totally blind.[15]

References

  1. ↑ Bateman JB, Klisak I, Kojis T, Mohandas T, Sparkes RS, Li TS, Applebury ML, Bowes C, Farber DB (Mar 1992). "Assignment of the beta-subunit of rod photoreceptor cGMP phosphodiesterase gene PDEB (homolog of the mouse rd gene) to human chromosome 4p16". Genomics. 12 (3): 601–3. doi:10.1016/0888-7543(92)90454-Z. PMID 1313787.
  2. ↑ 2.0 2.1 "Entrez Gene: PDE6B phosphodiesterase 6B, cGMP-specific, rod, beta (congenital stationary night blindness 3, autosomal dominant)".
  3. ↑ Wang Q, Chen Q, Zhao K, Wang L, Wang L, Traboulsi EI (2001). "Update on the molecular genetics of retinitis pigmentosa". Ophthalmic Genetics. 22 (3): 133–54. doi:10.1076/opge.22.3.133.2224. PMID 11559856.
  4. ↑ Danciger, M; Blaney, J; Gao, YQ; Zhao, DY; Heckenlively, JR; Jacobson, SG; Farber, DB (1 November 1995). "Mutations in the PDE6B gene in autosomal recessive retinitis pigmentosa". Genomics. 30 (1): 1–7. doi:10.1006/geno.1995.0001. PMID 8595886.
  5. ↑ "RetNet: Genes and Mapped Loci Causing Retinal Diseases". RetNet. Retrieved 12 May 2015.
  6. ↑ Han J, Dinculescu A, Dai X, Du W, Smith WC, Pang J (20 December 2013). "Review: the history and role of naturally occurring mouse models with Pde6b mutations". Molecular Vision. 19: 2579–89. PMC 3869645. PMID 24367157.
  7. ↑ 7.0 7.1 7.2 7.3 Cote RH (Jun 2004). "Characteristics of photoreceptor PDE (PDE6): similarities and differences to PDE5". International Journal of Impotence Research. 16 Suppl 1: S28–33. doi:10.1038/sj.ijir.3901212. PMID 15224133.
  8. ↑ Khramtsov NV, Feshchenko EA, Suslova VA, Shmukler BE, Terpugov BE, Rakitina TV, Atabekova NV, Lipkin VM (Aug 1993). "The human rod photoreceptor cGMP phosphodiesterase beta-subunit. Structural studies of its cDNA and gene". FEBS Letters. 327 (3): 275–8. doi:10.1016/0014-5793(93)81003-I. PMID 8394243.
  9. ↑ Anant JS, Ong OC, Xie HY, Clarke S, O'Brien PJ, Fung BK (Jan 1992). "In vivo differential prenylation of retinal cyclic GMP phosphodiesterase catalytic subunits". The Journal of Biological Chemistry. 267 (2): 687–90. PMID 1309771.
  10. ↑ 10.0 10.1 Farber DB, Lolley RN (1976). "Enzymic basis for cyclic GMP accumulation in degenerative photoreceptor cells of mouse retina". Journal of Cyclic Nucleotide Research. 2 (3): 139–48. PMID 6493.
  11. ↑ Keeler, CE (20 March 1928). "The Geotropic Reaction of Rodless Mice in LIght and in Darkness". The Journal of General Physiology. 11 (4): 361–8. doi:10.1085/jgp.11.4.361. PMC 2140980. PMID 19872404.
  12. ↑ Farber DB, Lolley RN (Nov 1974). "Cyclic guanosine monophosphate: elevation in degenerating photoreceptor cells of the C3H mouse retina". Science. 186 (4162): 449–51. doi:10.1126/science.186.4162.449. PMID 4369896.
  13. ↑ Chang B, Hawes NL, Hurd RE, Davisson MT, Nusinowitz S, Heckenlively JR (Feb 2002). "Retinal degeneration mutants in the mouse". Vision Research. 42 (4): 517–25. doi:10.1016/s0042-6989(01)00146-8. PMID 11853768.
  14. ↑ Bennett J, Tanabe T, Sun D, Zeng Y, Kjeldbye H, Gouras P, Maguire AM (Jun 1996). "Photoreceptor cell rescue in retinal degeneration (rd) mice by in vivo gene therapy". Nature Medicine. 2 (6): 649–54. doi:10.1038/nm0696-649. PMID 8640555.
  15. ↑ Petit L, Lhériteau E, Weber M, Le Meur G, Deschamps JY, Provost N, Mendes-Madeira A, Libeau L, Guihal C, Colle MA, Moullier P, Rolling F (Nov 2012). "Restoration of vision in the pde6β-deficient dog, a large animal model of rod-cone dystrophy". Molecular Therapy. 20 (11): 2019–30. doi:10.1038/mt.2012.134. PMC 3498794. PMID 22828504.

Further reading

  • Lerner LE, Piri N, Farber DB (2007). "Transcriptional and post-transcriptional regulation of the rod cGMP-phosphodiesterase beta-subunit gene. Recent advances and current concepts". Advances in Experimental Medicine and Biology. Advances in Experimental Medicine and Biology. 572: 217–29. doi:10.1007/0-387-32442-9_32. ISBN 978-0-387-28464-4. PMID 17249578.
  • Altherr MR, Wasmuth JJ, Seldin MF, Nadeau JH, Baehr W, Pittler SJ (Apr 1992). "Chromosome mapping of the rod photoreceptor cGMP phosphodiesterase beta-subunit gene in mouse and human: tight linkage to the Huntington disease region (4p16.3)". Genomics. 12 (4): 750–4. doi:10.1016/0888-7543(92)90305-C. PMID 1315306.
  • Collins C, Hutchinson G, Kowbel D, Riess O, Weber B, Hayden MR (Jul 1992). "The human beta-subunit of rod photoreceptor cGMP phosphodiesterase: complete retinal cDNA sequence and evidence for expression in brain". Genomics. 13 (3): 698–704. doi:10.1016/0888-7543(92)90144-H. PMID 1322354.
  • Catty P, Pfister C, Bruckert F, Deterre P (Sep 1992). "The cGMP phosphodiesterase-transducin complex of retinal rods. Membrane binding and subunits interactions". The Journal of Biological Chemistry. 267 (27): 19489–93. PMID 1326553.
  • Khramtsov NV, Feshchenko EA, Suslova VA, Terpugov BE, Rakitina TV, Atabekova NV, Shmukler BE, Lipkin VM (Dec 1992). "[Structural studies of cDNA and the gene for the beta-subunit of cGMP phosphodiesterase from human retina]". Bioorganicheskaia Khimiia. 18 (12): 1551–4. PMID 1338685.
  • Weber B, Riess O, Hutchinson G, Collins C, Lin BY, Kowbel D, Andrew S, Schappert K, Hayden MR (Nov 1991). "Genomic organization and complete sequence of the human gene encoding the beta-subunit of the cGMP phosphodiesterase and its localisation to 4p 16.3". Nucleic Acids Research. 19 (22): 6263–8. doi:10.1093/nar/19.22.6263. PMC 329137. PMID 1720239.
  • McLaughlin ME, Ehrhart TL, Berson EL, Dryja TP (Apr 1995). "Mutation spectrum of the gene encoding the beta subunit of rod phosphodiesterase among patients with autosomal recessive retinitis pigmentosa". Proceedings of the National Academy of Sciences of the United States of America. 92 (8): 3249–53. doi:10.1073/pnas.92.8.3249. PMC 42143. PMID 7724547.
  • Gal A, Orth U, Baehr W, Schwinger E, Rosenberg T (Aug 1994). "Heterozygous missense mutation in the rod cGMP phosphodiesterase beta-subunit gene in autosomal dominant stationary night blindness". Nature Genetics. 7 (4): 551. doi:10.1038/ng0894-551a. PMID 7951329.
  • Gal A, Orth U, Baehr W, Schwinger E, Rosenberg T (May 1994). "Heterozygous missense mutation in the rod cGMP phosphodiesterase beta-subunit gene in autosomal dominant stationary night blindness". Nature Genetics. 7 (1): 64–8. doi:10.1038/ng0594-64. PMID 8075643.
  • McLaughlin ME, Sandberg MA, Berson EL, Dryja TP (Jun 1993). "Recessive mutations in the gene encoding the beta-subunit of rod phosphodiesterase in patients with retinitis pigmentosa". Nature Genetics. 4 (2): 130–4. doi:10.1038/ng0693-130. PMID 8394174.
  • Valverde D, Solans T, Grinberg D, Balcells S, Vilageliu L, Bayés M, Chivelet P, Besmond C, Goossens M, González-Duarte R, Baiget M (Jan 1996). "A novel mutation in exon 17 of the beta-subunit of rod phosphodiesterase in two RP sisters of a consanguineous family". Human Genetics. 97 (1): 35–8. doi:10.1007/BF00218829. PMID 8557257.
  • Gao YQ, Danciger M, Zhao DY, Blaney J, Piriev NI, Shih J, Jacobson SG, Heckenlively JH, Farber DB (Feb 1996). "Screening of the PDE6B gene in patients with autosomal dominant retinitis pigmentosa". Experimental Eye Research. 62 (2): 149–54. doi:10.1006/exer.1996.0019. PMID 8698075.
  • Suslova VA, Suslov ON, Kim EE, Lipkin VM (Apr 1996). "[Organization of the gene for the beta-subunit of human photoreceptor cyclic GMP phosphodiesterase]". Bioorganicheskaia Khimiia. 22 (4): 256–63. PMID 8768262.
  • Valverde D, Baiget M, Seminago R, del Rio E, García-Sandoval B, del Rio T, Bayés M, Balcells S, Martínez A, Grinberg D, Ayuso C (1997). "Identification of a novel R552O mutation in exon 13 of the beta-subunit of rod phosphodiesterase gene in a Spanish family with autosomal recessive retinitis pigmentosa". Human Mutation. 8 (4): 393–4. doi:10.1002/humu.1380080403. PMID 8956055.

External links

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