Nucleoskeleton: Difference between revisions
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=Small proteins ([[polypeptide]]s)= | =Small proteins ([[polypeptide]]s)= | ||
The [[nuclear pore complex]] restricts the size of particles including molecules that can get into the [[ | 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,<ref name=Kramer>{{ cite journal |author=Kramer A, Ludwig Y, Shahin V, Oberleithner H |title=A Pathway Separate from the Central Channel through the Nuclear Pore Complex for Inorganic Ions and Small Macromolecules |journal=J Biol Chem. |volume=282 |issue=43 |pages=31437-43 |month=Oct |year=2007 |doi=10.1074/jbc.M703720200 |pmid=17726020 |url=http://www.jbc.org/cgi/content/full/282/43/31437 }}</ref> 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.<ref name=Melchior>{{ cite journal |author=Melchior F, Gerace L |title=Mechanisms of nuclear protein import |journal=Curr Opin Cell Biol. |volume=7 |issue=3 |month=Jun |year=1995 |pages=310-8 |pmid=7662359 }}</ref> | ||
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. For example, [[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]].<ref name=emerin>{{ cite web |title=Entrez Gene: EMD emerin |url=http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2010&ordinalpos=12&itool=EntrezSystem2.PEntrez.Gene.Gene_ResultsPanel.Gene_RVDocSum }}</ref><ref name=EMD>{{ cite web |title=GENATLAS: GENE Database EMD |url=http://genatlas.medecine.univ-paris5.fr/ }}</ref><ref name=EMERIN>{{ cite web |title=Apropos IpiRecord: IPI00032003 |url=http://apropos.mcw.edu/ipi_records/show/203523 }}</ref> | 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. For example, [[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]].<ref name=emerin>{{ cite web |title=Entrez Gene: EMD emerin |url=http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2010&ordinalpos=12&itool=EntrezSystem2.PEntrez.Gene.Gene_ResultsPanel.Gene_RVDocSum }}</ref><ref name=EMD>{{ cite web |title=GENATLAS: GENE Database EMD |url=http://genatlas.medecine.univ-paris5.fr/ }}</ref><ref name=EMERIN>{{ cite web |title=Apropos IpiRecord: IPI00032003 |url=http://apropos.mcw.edu/ipi_records/show/203523 }}</ref> | ||
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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. The structural elements include the nuclear lamina, core filaments, diffuse skeleton, nuclear bodies, the intranucleolar skeleton and fibrillar centers.
Small proteins (polypeptides)
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,[1] 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.[2]
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. For example, 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.[3][4][5]
Actin nucleoskeleton
Actins are highly conserved proteins that can form a tetramer. Further polymerization produces microfilaments such as those of the cytoskeleton. 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.[6] 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.[6] ACTR1A 42.6 kDa is a subunit of dynactin, as is ACTR1B 42.3 kDa. Both subunits are Arp1 (centractin). Arp2 45 kDa[7] is a major constituent of the Arp2/3 complex.[8] Arp3 47 kDa[9] is a major constituent of the Arp2/3 complex[10] which binds actin and may initiate nucleus assembly of actin.[11] Arp5 68 kDa[12] has no NLS but is involved in ATP-dependent chromatin remodeling.[13] Arp6 20 kDa and 36 kDa forms[14] has nuclear localization[15]. Arp8 58 kDa[16], 37 kDa and 70 kDa[17] chromosome associates[18] with involvement in chromatin remodelling (has NLS).[19] Arp10 46 kDa[20]. ArpM1 41 kDa[21]. 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[22]. Actin-like 6B (ACTL6B) is an Arp, a subunit of the BAF complex, which is functionally related to SWI/SNF complex, 47 kDa[23], and has intracellular nucleus localization[24]. 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.[25] It is a structural constituent of the nucleoskeleton.[26] ACTRT1 42 kDa[27]. ACTRT2 42 kDa[28].
Dynactin 1 (Dctn1) 150 kDa, the largest subunit of dynactin, which binds microtubules and is involved in chromosome movement, interacts with dynein.[29] And, it has a NLS, is microtubule plus-end binding[30], has a second isoform of 135 kDa[31], and binds to Arp1.[32] 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[33]. Dynactin 4 (Dctn4) 52 kDa is intracellular to the nucleus and a member of the pointed-end complex which contains Dctn4-6 and ACTR10.[34] Dynactin 5 20 kDa and dynactin 6 21 kDa.
Proteins
Proteins larger than those allowed through a nuclear pore by passive transport require a nuclear localization signal (NLS). This is an amino acid sequence that targets the cytosolic nuclear transport receptors of the nuclear pore complex. A nuclear import NLS will bind strongly to importin, while an export NLS (nuclear export signal, NES) binds to an exportin.
The lamins of mammalian nuclei are polypeptides of 60-80 kDa: A (70 kDa), B (68 kDa), and C (60 kDa).[35] A- and B-type lamins, which form separate, but interacting, stable meshworks in the lamina, have different mobilities.[36] All of the lamins have a NLS.[37]
Structures
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.
Nuclear matrix
Still others such as the nuclear matrix[38][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.[36]
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.[43]
Intranuclear structures
In addition to forming the nuclear lamina, the lamins can form intranuclear structures.[43]
References
- ↑ 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) - ↑ "Entrez Gene: EMD emerin".
- ↑ "GENATLAS: GENE Database EMD".
- ↑ "Apropos IpiRecord: IPI00032003".
- ↑ 6.0 6.1 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".
- ↑ "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".
- ↑ Klaus Urich (1994). Comparative Animal Biochemistry. Springer. p. 359. ISBN 3540574204, 9783540574200 Check
|isbn=value: invalid character (help). - ↑ 36.0 36.1 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".
- ↑ Nickerson J (2001). "Experimental observations of a nuclear matrix". J. Cell. Sci. 114 (Pt 3): 463–74. PMID 11171316. Unknown parameter
|month=ignored (help) - ↑ 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.
- ↑ 43.0 43.1 Broers JL, Hutchison CJ, Ramaekers FC (2004). "Laminopathies". J Pathol. 204 (4): 478–88. PMID 15495262. Unknown parameter
|month=ignored (help)