Nucleoskeleton: Difference between revisions
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Supervillin ([[SVIL]]) has NLSs contained in its amino-terminus. The carboxy-terminus contains numerous consecutive sequences with extensive similarity to proteins in the gelsolin family of actin-binding proteins, which cap, nucleate, and/or sever actin filaments. SVIL is tightly associated with both actin filaments and plasma membranes,<ref name=Pestonjamasp>{{ cite journal |author=Pestonjamasp KN, Pope RK, Wulfkuhle JD, Luna EJ |title=Supervillin (p205): A novel membrane-associated, F-actin-binding protein in the villin/gelsolin superfamily. |journal=J. Cell Biol. |volume=139 |issue= 5 |pages= 1255-69 |year= 1997 |pmid= 9382871 |doi= }}</ref> suggesting a role as a high-affinity link between the actin cytoskeleton and the membrane. Its function may include recruitment of actin and other cytoskeletal proteins into specialized structures at the plasma membrane and in the nuclei of growing cells.<ref name=supervillin>{{cite web | title = Entrez Gene: SVIL supervillin| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6840| accessdate = }}</ref> | Supervillin ([[SVIL]]) has NLSs contained in its amino-terminus. The carboxy-terminus contains numerous consecutive sequences with extensive similarity to proteins in the gelsolin family of actin-binding proteins, which cap, nucleate, and/or sever actin filaments. SVIL is tightly associated with both actin filaments and plasma membranes,<ref name=Pestonjamasp>{{ cite journal |author=Pestonjamasp KN, Pope RK, Wulfkuhle JD, Luna EJ |title=Supervillin (p205): A novel membrane-associated, F-actin-binding protein in the villin/gelsolin superfamily. |journal=J. Cell Biol. |volume=139 |issue= 5 |pages= 1255-69 |year= 1997 |pmid= 9382871 |doi= }}</ref> suggesting a role as a high-affinity link between the actin cytoskeleton and the membrane. Its function may include recruitment of actin and other cytoskeletal proteins into specialized structures at the plasma membrane and in the nuclei of growing cells.<ref name=supervillin>{{cite web | title = Entrez Gene: SVIL supervillin| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=6840| accessdate = }}</ref> | ||
SVIL is known to localize to chromosomes.<ref name=Pope>{{cite journal | author=Pope RK, Pestonjamasp KN, Smith KP, ''et al.'' |title=Cloning, characterization, and chromosomal localization of human supervillin (SVIL). |journal=Genomics |volume=52 |issue= 3 |pages= 342-51 |year= 1998 |pmid= 9867483 |doi= }}</ref> It also bundles F-actin.<ref name=Wulfkuhle>{{cite journal | author=Wulfkuhle JD, Donina IE, Stark NH, ''et al.'' |title=Domain analysis of supervillin, an F-actin bundling plasma membrane protein with functional nuclear localization signals. |journal=J. Cell. Sci. |volume=112 ( Pt 13) |issue= |pages= 2125-36 |year= 1999 |pmid= 10362542 |doi= }}</ref> And, binds myosin II which is in the nucleus.<ref name=Chen>{{cite journal | author=Chen Y, Takizawa N, Crowley JL, ''et al.'' |title=F-actin and myosin II binding domains in supervillin. |journal=J. Biol. Chem. |volume=278 |issue= 46 |pages= 46094-106 |year= 2003 |pmid= 12917436 |doi= 10.1074/jbc.M305311200 }}</ref> | SVIL is known to localize to chromosomes.<ref name=Pope>{{cite journal | author=Pope RK, Pestonjamasp KN, Smith KP, ''et al.'' |title=Cloning, characterization, and chromosomal localization of human supervillin (SVIL). |journal=Genomics |volume=52 |issue= 3 |pages= 342-51 |year= 1998 |pmid= 9867483 |doi= }}</ref> It also bundles F-actin.<ref name=Wulfkuhle>{{cite journal | author=Wulfkuhle JD, Donina IE, Stark NH, ''et al.'' |title=Domain analysis of supervillin, an F-actin bundling plasma membrane protein with functional nuclear localization signals. |journal=J. Cell. Sci. |volume=112 ( Pt 13) |issue= |pages= 2125-36 |year= 1999 |pmid= 10362542 |doi= }}</ref> And, binds myosin II which is not in the nucleus.<ref name=Chen>{{cite journal | author=Chen Y, Takizawa N, Crowley JL, ''et al.'' |title=F-actin and myosin II binding domains in supervillin. |journal=J. Biol. Chem. |volume=278 |issue= 46 |pages= 46094-106 |year= 2003 |pmid= 12917436 |doi= 10.1074/jbc.M305311200 }}</ref> | ||
One motor protein that localizes intracellularly to the nucleus is myosin 1F ({{Gene|MYO1F}}) 125 kDa.<ref name=MYO1F>{{ cite web |title=GENATLAS : GENE Database MYO1F |url=http://genatlas.medecine.univ-paris5.fr/ }}</ref> It does not have a NLS. Its N terminal motor domain uses ATP and has actin binding sites.<ref name=MYO1F/> The tail of MYO1F includes (1) a TH-1 region which may interact with membrane phospholipids, (2) a TH-2 proline-rich region which may contain an ATP-insensitive actin-binding site, and (3) a SH-3 domain found in a variety of cytoskeletal and signaling proteins.<ref name=Crozet>{{ cite journal |author=Crozet F, el Amraoui A, Blanchard S, Lenoir M, Ripoll C, Vago P, Hamel C, Fizames C, Levi-Acobas F, Depétris D, Mattei MG, Weil D, Pujol R, Petit C |title=Cloning of the genes encoding two murine and human cochlear unconventional type I myosins |journal=Genomics. |year=1997 |month=Mar |volume=40 |issue=2 |pages=332-41 |pmid=9119401 }}>/ref> | |||
=[[Nuclear matrix]]= | =[[Nuclear matrix]]= | ||
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Editor-In-Chief: Henry A. Hoff
The nucleoskeleton (NSK) provides a framework for DNA replication, transcription, chromatin remodeling, signaling, and mRNA synthesis, processing and transport.
Introduction
Of the structures local to the nucleoplasm, some serve to confine it such as the inner membrane of the nuclear envelope. While others are completely suspended within it, for example, the nucleolus.
Other structural elements include the nuclear lamina, core filaments, diffuse skeleton, nuclear bodies, the intranucleolar skeleton and fibrillar centers.
Nuclear envelope membrane skeleton
Emerin 18 kDa (no NLS) mediates inner nuclear membrane anchorage to the nuclear lamina, regulates the flux of beta-catenin into the nucleus, and interacts with nuclear actin.[1][2][3]
Nuclear lamina
The nuclear lamina is a dense, ~ 30 to 100 nanometers thick, fibrillar network composed of intermediate filaments made of lamin that lines the inner surface of the nuclear envelope in animal cells.
The nuclear pore complexes are embedded in the nuclear lamina.[4]
Nuclear pore complex
The nuclear pore complex restricts the size of particles including molecules that can get into the nucleoplasm to be incorporated into the nucleoskeleton. Larger proteins require a nuclear localization signal (NLS). The pores are 100 nm in total diameter, with an opening diameter of about 50 nm; however, the gap through which molecules freely diffuse is only about 9-10 nm wide,[5] due to the presence of regulatory systems within the center of the pore. The 10 nm diameter corresponds to an upper mass limit of 70 kDa.[6]
Due to the size limitation of the nuclear pore, these polypeptides would range from 9 kDa to <70 kDa and not need or have a NLS.
The lamins of mammalian nuclei are polypeptides of 60-80 kDa: A (70 kDa), B (68 kDa), and C (60 kDa).[7] A- and B-type lamins, which form separate, but interacting, stable meshworks in the lamina, have different mobilities.[8] All of the lamins have a NLS.[9]
Actin nucleoskeleton
Actins are highly conserved proteins that can form a tetramer. Further polymerization produces microfilaments such as those of the cytoskeleton.
Nuclear actins
Alpha actin: ACTA1 42 kDa is myosin binding and forms actin microfilaments, ACTA2 42 kDa is at least intracellular. As a part of nuclear actin, beta-actin (ACTB) has a 42 kDa mass as a monomer (no NLS), is a component of SWI/SNF chromatin remodeling complexes, and rapidly shuttles between the nucleosol and cytosol.[10] Gamma actin: ACTC1 42 kDa is intracellular, incorporated into actin microfilaments, is dissolved in the cytosol.
The actin-related proteins (Arps) are also components of these chromatin remodeling complexes.[10] ACTR1A 42.6 kDa is a subunit of dynactin, as is ACTR1B 42.3 kDa. Both subunits are Arp1 (centractin). Arp2 45 kDa[11] is a major constituent of the Arp2/3 complex.[12] Arp3 47 kDa[13] is a major constituent of the Arp2/3 complex[14] which binds actin and may initiate nucleus assembly of actin.[15] Arp5 68 kDa[16] has no NLS but is involved in ATP-dependent chromatin remodeling.[17] Arp6 20 kDa and 36 kDa forms[18] has nuclear localization[19]. Arp8 58 kDa[20], 37 kDa and 70 kDa[21] chromosome associates[22] with involvement in chromatin remodelling (has NLS).[23] Arp10 46 kDa[24]. ArpM1 41 kDa[25]. The Arp2/3 complex may be involved in the control of actin polymerization. ARPC1A 41 kDa is a subunit of the Arp2/3 complex along with ARPC1B 41 kDa, ARPC2 34 kDa, ARPC3 21 kDa, ARPC3B 21 kDa, ARPC4 20 kDa, ARPC5 16 kDa, and ARPC5L 17 kDa[26].
Nuclear actin-like proteins (ACTLs)
Actin-like 6B (ACTL6B) is an Arp, a subunit of the BAF complex, which is functionally related to SWI/SNF complex, 47 kDa[27], and has intracellular nucleus localization[28]. As with ACTL6B, ACTL6A 53 kDa and 43 kDa (two different isoforms) binds chromatin, localizes to the nucleus, is involved in chromatin remodeling, and transcription.[29] It is a structural constituent of the nucleoskeleton.[30] ACTRT1 42 kDa[31]. ACTRT2 42 kDa[32].
Nuclear actin binding proteins (ABPs)
Supervillin (SVIL) has NLSs contained in its amino-terminus. The carboxy-terminus contains numerous consecutive sequences with extensive similarity to proteins in the gelsolin family of actin-binding proteins, which cap, nucleate, and/or sever actin filaments. SVIL is tightly associated with both actin filaments and plasma membranes,[33] suggesting a role as a high-affinity link between the actin cytoskeleton and the membrane. Its function may include recruitment of actin and other cytoskeletal proteins into specialized structures at the plasma membrane and in the nuclei of growing cells.[34]
SVIL is known to localize to chromosomes.[35] It also bundles F-actin.[36] And, binds myosin II which is not in the nucleus.[37]
One motor protein that localizes intracellularly to the nucleus is myosin 1F (MYO1F) 125 kDa.[38] It does not have a NLS. Its N terminal motor domain uses ATP and has actin binding sites.[38] The tail of MYO1F includes (1) a TH-1 region which may interact with membrane phospholipids, (2) a TH-2 proline-rich region which may contain an ATP-insensitive actin-binding site, and (3) a SH-3 domain found in a variety of cytoskeletal and signaling proteins.[39] are found throughout the inside of the nucleus.
Nucleoplasmic veil
Lamins within the nucleoplasm form another regular structure the nucleoplasmic veil[40]. The veil is excluded from the nucleolus and is present during interphase.[41] The lamin structures that make up the veil bind chromatin and disrupting their structure inhibits transcription of protein-coding genes.[42] Changes also occur in the lamina mesh size.[8]
Intranuclear structures
In addition to forming the nuclear lamina, the lamins can form intranuclear structures.[4]
Microtubular structures
Dynactin 1 (Dctn1) 150 kDa, the largest subunit of dynactin, which binds microtubules and is involved in chromosome movement, interacts with dynein.[43] And, it has a NLS, is microtubule plus-end binding[44], has a second isoform of 135 kDa[45], and binds to Arp1.[46] Dynactin 2 (dynamitin) 50 kDa, 4-5 copies per dynactin molecule, is intracellular to the nucleus. Dynactin 3 22 kDa is a part of the dynactin complex, binding directly to Dctn1, and is intra cellular to the nucleus[47]. Dynactin 4 (Dctn4) 52 kDa is intracellular to the nucleus and a member of the pointed-end complex which contains Dctn4-6 and ACTR10.[48] Dynactin 5 20 kDa and dynactin 6 21 kDa.
Nucleolar skeleton
Nucleolar skeletons are observable with light and electron microscopy and are characterized by ravels of filaments that are especially densely packed in the nucleolar cortex.[49]
DNA as well as RNA are not constituents of this structure.
This insoluble protein filament complex may form a skeleton specific to the nucleolus proper that is different from other extraction-resistant components of the nucleus such as the matrix and lamina and is involved in the spatial organization of the nucleolar chromatin and its transcriptional products.<ref name=Franke> It is a framework of nucleolar filaments. The nucleolar skeletons are roughly spheroidal like the nucleolus itself and constitute the nucleolar cortex. The interior is formed by relatively loosely packed tangles of filaments ~4 nm thick arranged in higher-order coils of 30-40 nm dia. In the periphery are aggregates of various sizes representing local ravels of filament packing, with many filament continuities to internal filament elements.
The skeleton contains considerable amounts of nuclear actin. The fibrillar meshworks indistinguishable from the nucleolar skeleton structure are also observable in anucleolate mutants, forming so-called “pseudo-nucleoli” suggesting that such skeletal proteins can assemble into spheroidal meshwork structures independent of the presence of nucleolar chromatin.<ref name=Franke>
References
- ↑ "Entrez Gene: EMD emerin".
- ↑ "GENATLAS: GENE Database EMD".
- ↑ "Apropos IpiRecord: IPI00032003".
- ↑ 4.0 4.1 Broers JL, Hutchison CJ, Ramaekers FC (2004). "Laminopathies". J Pathol. 204 (4): 478–88. PMID 15495262. Unknown parameter
|month=ignored (help) - ↑ Kramer A, Ludwig Y, Shahin V, Oberleithner H (2007). "A Pathway Separate from the Central Channel through the Nuclear Pore Complex for Inorganic Ions and Small Macromolecules". J Biol Chem. 282 (43): 31437–43. doi:10.1074/jbc.M703720200. PMID 17726020. Unknown parameter
|month=ignored (help) - ↑ Melchior F, Gerace L (1995). "Mechanisms of nuclear protein import". Curr Opin Cell Biol. 7 (3): 310–8. PMID 7662359. Unknown parameter
|month=ignored (help) - ↑ Klaus Urich (1994). Comparative Animal Biochemistry. Springer. p. 359. ISBN 3540574204, 9783540574200 Check
|isbn=value: invalid character (help). - ↑ 8.0 8.1 Shimi T, Pfleghaar K, Kojima S, Pack CG, Solovei I, Goldman AE, Adam SA, Shumaker DK, Kinjo M, Cremer T, Goldman RD (2008). "The A- and B-type nuclear lamin networks: microdomains involved in chromatin organization and transcription". Genes Dev. 22 (24): 3409–21. PMID 19141474. Unknown parameter
|month=ignored (help) - ↑ "GENATLAS: Gene Database".
- ↑ 10.0 10.1 Olave IA, Reck-Peterson SL, Crabtree GR (2002). "Olave IA, Reck-Peterson SL, Crabtree GR". Annu Rev Biochem. 71: 755–81. PMID 12045110.
- ↑ "Apropos IpiRecord: IPI00005159 - ACTR2".
- ↑ "Entrez Gene: ACTR2 ARP2 actin-related protein 2 homolog (yeast)".
- ↑ "Apropos IpiRecord: IPI00007068".
- ↑ "Entrez Gene: ACTR3 ARP3 actin-related protein 3 homolog".
- ↑ Kelly AE, Kranitz H, Dötsch V, Mullins RD (2006). "Actin binding to the central domain of WASP/Scar proteins plays a critical role in the activation of the Arp2/3 complex". J Biol Chem. (15): 10589–97. PMID 16403731. Unknown parameter
|month=ignored (help); Unknown parameter|volum=ignored (help) - ↑ "Human Protein Atlas ACTR5 gene information".
- ↑ "Nuclear Protein Database ARP5".
- ↑ "Apropos IpiRecord: IPI00171779".
- ↑ Ohfuchi E, Kato M, Sasaki M, Sugimoto K, Oma Y, Harata M (2006). "Vertebrate Arp6, a novel nuclear actin-related protein, interacts with heterochromatin protein 1". Eur J Cell Biol. 85 (5): 411–21. PMID 16487625. Unknown parameter
|month=ignored (help) - ↑ "Apropos Ipirecord: IPI00025646".
- ↑ "Human Protein Atlas ACTR8 gene information".
- ↑ "Entrez Gene: ACTR8 ARP8 actin-related protein 8 homolog (yeast)".
- ↑ "Nuclear Protein Database ARP8".
- ↑ "Human Protein Atlas ACTR10 gene information".
- ↑ "GENATLAS : GENE Database ARPM1".
- ↑ "GENATLAS : GENE Database ARPC5L".
- ↑ "Human Protein Atlas ACTL6B gene information".
- ↑ "GENATLAS : GENE Database ACTL6B".
- ↑ "Human Protein Atlas ACTL6A gene information".
- ↑ "GENATLAS : GENE Database ACTL6A".
- ↑ "Human Protein Atlas ACTRT1 gene information".
- ↑ "Human Protein Atlas ACTRT2 gene information".
- ↑ Pestonjamasp KN, Pope RK, Wulfkuhle JD, Luna EJ (1997). "Supervillin (p205): A novel membrane-associated, F-actin-binding protein in the villin/gelsolin superfamily". J. Cell Biol. 139 (5): 1255–69. PMID 9382871.
- ↑ "Entrez Gene: SVIL supervillin".
- ↑ Pope RK, Pestonjamasp KN, Smith KP; et al. (1998). "Cloning, characterization, and chromosomal localization of human supervillin (SVIL)". Genomics. 52 (3): 342–51. PMID 9867483.
- ↑ Wulfkuhle JD, Donina IE, Stark NH; et al. (1999). "Domain analysis of supervillin, an F-actin bundling plasma membrane protein with functional nuclear localization signals". J. Cell. Sci. 112 ( Pt 13): 2125–36. PMID 10362542.
- ↑ Chen Y, Takizawa N, Crowley JL; et al. (2003). "F-actin and myosin II binding domains in supervillin". J. Biol. Chem. 278 (46): 46094–106. doi:10.1074/jbc.M305311200. PMID 12917436.
- ↑ 38.0 38.1 "GENATLAS : GENE Database MYO1F".
- ↑ Tetko IV, Haberer G, Rudd S, Meyers B, Mewes HW, Mayer KF (2006). "Spatiotemporal expression control correlates with intragenic scaffold matrix attachment regions (S/MARs) in Arabidopsis thaliana". PLoS Comput. Biol. 2 (3): e21. doi:10.1371/journal.pcbi.0020021. PMC 1420657. PMID 16604187. Unknown parameter
|month=ignored (help) - ↑ Goldman R, Gruenbaum Y, Moir R, Shumaker D, Spann T (2002). "Nuclear lamins: building blocks of nuclear architecture". Genes Dev. 16 (5): 533–547. doi:10.1101/gad.960502. PMID 11877373.
- ↑ Moir RD, Yoona M, Khuona S, Goldman RD. (2000). "Nuclear Lamins A and B1: Different Pathways of Assembly during Nuclear Envelope Formation in Living Cells". Journal of Cell Biology. 151 (6): 1155–1168. doi:10.1083/jcb.151.6.1155. PMID 11121432.
- ↑ Spann TP, Goldman AE, Wang C, Huang S, Goldman RD (2002). "Alteration of nuclear lamin organization inhibits RNA polymerase II–dependent transcription". J of Cell Biol. 156 (4): 603–608. doi:10.1083/jcb.200112047. PMID 11854306.
- ↑ "Entrez Gene: DCTN1 dynactin 1 (p150, glued homolog, Drosophila)".
- ↑ "Nuclear Protein Database dynactin 1".
- ↑ "Apropos IpiRecord: IPI00029485 - DCTN1, ISOFORM P150 OF DYNACTIN SUBUNIT 1".
- ↑ "GENATLAS : GENE Database DCTN1".
- ↑ "GENATLAS : GENE Database DCTN3".
- ↑ "GENATLAS : GENE Database DCTN4".
- ↑ Franke WW, Kleinschmidt JA, Spring H, Krohne G, Grund C, Trendelenburg MF, Stoehr M, Scheer U (1981). "A nucleolar skeleton of protein filaments demonstrated in amplified nucleoli of Xenopus laevis". J Cell Biol. 90 (2): 289–99. PMID 2111883. Unknown parameter
|month=ignored (help)