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CAPZB is a member of the [[F-actin capping protein]] family. This gene encodes the beta subunit of the barbed-end actin binding protein.  The protein regulates growth of the actin filament by capping the barbed end of growing actin filaments.<ref name = "entrez"/>
CAPZB is a member of the [[F-actin capping protein]] family. This gene encodes the beta subunit of the barbed-end actin binding protein.  The protein regulates growth of the actin filament by capping the barbed end of growing actin filaments.<ref name = "entrez"/>


CapZβ functions to cap [[actin]] filaments at barbed (+) ends, thus controlling the rate of [[actin|G-actin]] polymerization to [[actin|F-actin]] and corresponding filament length. CapZ works in concert with [[tropomodulin]], which caps actin at pointed ends. In muscle, the interaction of CapZ with [[actin]] is critical during myofibrilogenesis, as administration of a CapZ monoclonal antibody or expression of CapZ mutant protein disrupts actin filament formation and assembly of myofibrils.<ref name = "Schafer_1995"/> Isoforms of the CapZβ (β1 and β2) have distinct functions, as CapZβ1 anchors [[actin]] at [[sarcomere|Z-discs]] and CapZβ2 at [[intercalated disc]]s.<ref name = "Papa_1999"/><ref name = "Hart_1999"/> Overexpression of CapZβ2 (and concomitant down-regulation of CapZβ1) in mice resulted in a diseased phenotype with stunted growth, irregular gait, labored breathing and juvenile lethality. Ultrastructural measurements showed severely disrupted myofibrillar architecture.<ref name = "Hart_1999">{{cite journal | vauthors = Hart MC, Cooper JA | title = Vertebrate isoforms of actin capping protein beta have distinct functions In vivo | journal = The Journal of Cell Biology | volume = 147 | issue = 6 | pages = 1287–98 | date = December 1999 | pmid = 10601341 | doi = 10.1083/jcb.147.6.1287 | pmc=2168092}}</ref> A function of CapZβ in transducing [[protein kinase C]] signaling in [[cardiac myocytes]] was illuminated by a study in skinned cardiac fibers which demonstrated that partial, transgenic reduction of CapZβ attenuated the functional effect of [[protein kinase C]] on contraction and disturbed normal PKC isoform translocation patterns following [[phenylephrine]] or [[endothelin-1]] treatment.<ref>{{cite journal | vauthors = Pyle WG, Hart MC, Cooper JA, Sumandea MP, de Tombe PP, Solaro RJ | title = Actin capping protein: an essential element in protein kinase signaling to the myofilaments | journal = Circulation Research | volume = 90 | issue = 12 | pages = 1299–306 | date = June 2002 | pmid = 12089068 | doi = 10.1161/01.res.0000024389.03152.22 }}</ref> Interestingly, a later study showed that partial reduction of CapZβ was cardioprotective during ischemia-reperfusion injury, concomitant with altered PKC isoform translocation to [[myofilament]]s.<ref>{{cite journal | vauthors = Yang FH, Pyle WG | title = Reduced cardiac CapZ protein protects hearts against acute ischemia-reperfusion injury and enhances preconditioning | journal = Journal of Molecular and Cellular Cardiology | volume = 52 | issue = 3 | pages = 761–72 | date = March 2012 | pmid = 22155006 | doi = 10.1016/j.yjmcc.2011.11.013 }}</ref> Regarding the turnover of CapZβ, it was recently demonstrated that the protein turnover of CapZβ1 is in part regulated by the Bcl-2–associated athanogene, [[BAG3]], through a mechanism involving the association between [[HSC70]] and CapZβ1.<ref name = "Hishiya_2010"/>
CapZβ functions to cap [[actin]] filaments at barbed (+) ends, thus controlling the rate of [[actin|G-actin]] polymerization to [[actin|F-actin]] and corresponding filament length. CapZ works in concert with [[tropomodulin]], which caps actin at pointed ends. In muscle, the interaction of CapZ with [[actin]] is critical during myofibrilogenesis, as administration of a CapZ monoclonal antibody or expression of CapZ mutant protein disrupts actin filament formation and assembly of myofibrils.<ref name = "Schafer_1995"/> Isoforms of the CapZβ (β1 and β2) have distinct functions, as CapZβ1 anchors [[actin]] at [[sarcomere|Z-discs]] and CapZβ2 at [[intercalated disc]]s.<ref name = "Papa_1999"/><ref name = "Hart_1999"/> Overexpression of CapZβ2 (and concomitant down-regulation of CapZβ1) in mice resulted in a diseased phenotype with stunted growth, irregular gait, labored breathing and juvenile lethality. Ultrastructural measurements showed severely disrupted myofibrillar architecture.<ref name = "Hart_1999">{{cite journal | vauthors = Hart MC, Cooper JA | title = Vertebrate isoforms of actin capping protein beta have distinct functions In vivo | journal = The Journal of Cell Biology | volume = 147 | issue = 6 | pages = 1287–98 | date = December 1999 | pmid = 10601341 | doi = 10.1083/jcb.147.6.1287 | pmc=2168092}}</ref> A function of CapZβ in transducing [[protein kinase C]] signaling in [[cardiac myocytes]] was illuminated by a study in skinned cardiac fibers which demonstrated that partial, transgenic reduction of CapZβ attenuated the functional effect of [[protein kinase C]] on contraction and disturbed normal PKC isoform translocation patterns following [[phenylephrine]] or [[endothelin-1]] treatment.<ref>{{cite journal | vauthors = Pyle WG, Hart MC, Cooper JA, Sumandea MP, de Tombe PP, Solaro RJ | title = Actin capping protein: an essential element in protein kinase signaling to the myofilaments | journal = Circulation Research | volume = 90 | issue = 12 | pages = 1299–306 | date = June 2002 | pmid = 12089068 | doi = 10.1161/01.res.0000024389.03152.22 }}</ref> A later study showed that partial reduction of CapZβ was cardioprotective during ischemia-reperfusion injury, concomitant with altered PKC isoform translocation to [[myofilament]]s.<ref>{{cite journal | vauthors = Yang FH, Pyle WG | title = Reduced cardiac CapZ protein protects hearts against acute ischemia-reperfusion injury and enhances preconditioning | journal = Journal of Molecular and Cellular Cardiology | volume = 52 | issue = 3 | pages = 761–72 | date = March 2012 | pmid = 22155006 | doi = 10.1016/j.yjmcc.2011.11.013 }}</ref> Regarding the turnover of CapZβ, it was recently demonstrated that the protein turnover of CapZβ1 is in part regulated by the Bcl-2–associated athanogene, [[BAG3]], through a mechanism involving the association between [[HSC70]] and CapZβ1.<ref name = "Hishiya_2010"/>


==Clinical Significance==
==Clinical Significance==
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<ref name = "Hishiya_2010">{{cite journal | vauthors = Hishiya A, Kitazawa T, Takayama S | title = BAG3 and Hsc70 interact with actin capping protein CapZ to maintain myofibrillar integrity under mechanical stress | journal = Circulation Research | volume = 107 | issue = 10 | pages = 1220–31 | date = November 2010 | pmid = 20884878 | doi = 10.1161/CIRCRESAHA.110.225649 | pmc=2980587}}</ref>
<ref name = "Hishiya_2010">{{cite journal | vauthors = Hishiya A, Kitazawa T, Takayama S | title = BAG3 and Hsc70 interact with actin capping protein CapZ to maintain myofibrillar integrity under mechanical stress | journal = Circulation Research | volume = 107 | issue = 10 | pages = 1220–31 | date = November 2010 | pmid = 20884878 | doi = 10.1161/CIRCRESAHA.110.225649 | pmc=2980587}}</ref>


<ref name = "Papa_1999">{{cite journal | vauthors = Papa I, Astier C, Kwiatek O, Raynaud F, Bonnal C, Lebart MC, Roustan C, Benyamin Y | title = Alpha actinin-CapZ, an anchoring complex for thin filaments in Z-line | journal = Journal of Muscle Research and Cell Motility | volume = 20 | issue = 2 | pages = 187–97 | date = February 1999 | pmid = 10412090 }}</ref>
<ref name = "Papa_1999">{{cite journal | vauthors = Papa I, Astier C, Kwiatek O, Raynaud F, Bonnal C, Lebart MC, Roustan C, Benyamin Y | title = Alpha actinin-CapZ, an anchoring complex for thin filaments in Z-line | journal = Journal of Muscle Research and Cell Motility | volume = 20 | issue = 2 | pages = 187–97 | date = February 1999 | pmid = 10412090 | doi = 10.1023/A:1005489319058 }}</ref>


<ref name = "Schafer_1994">{{cite journal | vauthors = Schafer DA, Korshunova YO, Schroer TA, Cooper JA | title = Differential localization and sequence analysis of capping protein beta-subunit isoforms of vertebrates | journal = The Journal of Cell Biology | volume = 127 | issue = 2 | pages = 453–65 | date = October 1994 | pmid = 7929588 | doi = 10.1083/jcb.127.2.453 | pmc=2120197}}</ref>
<ref name = "Schafer_1994">{{cite journal | vauthors = Schafer DA, Korshunova YO, Schroer TA, Cooper JA | title = Differential localization and sequence analysis of capping protein beta-subunit isoforms of vertebrates | journal = The Journal of Cell Biology | volume = 127 | issue = 2 | pages = 453–65 | date = October 1994 | pmid = 7929588 | doi = 10.1083/jcb.127.2.453 | pmc=2120197}}</ref>

Latest revision as of 17:42, 3 August 2018

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Ensembl

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UniProt

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RefSeq (mRNA)

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RefSeq (protein)

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Location (UCSC)n/an/a
PubMed searchn/an/a
Wikidata
View/Edit Human

F-actin-capping protein subunit beta, also known as CapZβ is a protein that in humans is encoded by the CAPZB gene.[1] CapZβ functions to cap actin filaments at barbed ends in muscle and other tissues.

Structure

CapZβ can exist as 3 unique β subunits, dependent on alternative splicing mechanisms.[2][3][4][5] CapZβ1 is 31.4 kDa and 277 amino acids in length, CapZβ2 is 30.6 kDa and 272 amino acids in length, and CapZβ3 is 301 amino acids in length (N-terminal extension of 29 amino acids relative to the β2 subunit.[3]). In contrast, the 3 α subunits arise from distinct genes.[6] CapZ is a heterodimer composed of an α and β subunit. In muscle, capping protein α1 subunit and β1 subunit are localized at the Z-disc, and form CapZ.[7] CapZ interacts with α-actinin, nebulette, nebulin, HSC70.[8] at the Z-disc.

Function

CAPZB is a member of the F-actin capping protein family. This gene encodes the beta subunit of the barbed-end actin binding protein. The protein regulates growth of the actin filament by capping the barbed end of growing actin filaments.[1]

CapZβ functions to cap actin filaments at barbed (+) ends, thus controlling the rate of G-actin polymerization to F-actin and corresponding filament length. CapZ works in concert with tropomodulin, which caps actin at pointed ends. In muscle, the interaction of CapZ with actin is critical during myofibrilogenesis, as administration of a CapZ monoclonal antibody or expression of CapZ mutant protein disrupts actin filament formation and assembly of myofibrils.[9] Isoforms of the CapZβ (β1 and β2) have distinct functions, as CapZβ1 anchors actin at Z-discs and CapZβ2 at intercalated discs.[10][11] Overexpression of CapZβ2 (and concomitant down-regulation of CapZβ1) in mice resulted in a diseased phenotype with stunted growth, irregular gait, labored breathing and juvenile lethality. Ultrastructural measurements showed severely disrupted myofibrillar architecture.[11] A function of CapZβ in transducing protein kinase C signaling in cardiac myocytes was illuminated by a study in skinned cardiac fibers which demonstrated that partial, transgenic reduction of CapZβ attenuated the functional effect of protein kinase C on contraction and disturbed normal PKC isoform translocation patterns following phenylephrine or endothelin-1 treatment.[12] A later study showed that partial reduction of CapZβ was cardioprotective during ischemia-reperfusion injury, concomitant with altered PKC isoform translocation to myofilaments.[13] Regarding the turnover of CapZβ, it was recently demonstrated that the protein turnover of CapZβ1 is in part regulated by the Bcl-2–associated athanogene, BAG3, through a mechanism involving the association between HSC70 and CapZβ1.[8]

Clinical Significance

There is currently little to no data available on the relationship between the CAPZB gene and human disease.

Model organisms

Model organisms have been used in the study of CAPZB function. A conditional knockout mouse line, called Capzbtm1a(EUCOMM)Wtsi[20][21] was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.[22][23][24]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[18][25] Twenty three tests were carried out on mutant mice and four significant abnormalities were observed.[18] No homozygous mutant embryos were identified during gestation, and therefore none survived until weaning. The remaining tests were carried out on heterozygous mutant adult mice and decreased circulating triglyceride levels were observed in female animals, while males displayed abnormal behaviour in an open field.[18]

References

  1. ↑ 1.0 1.1 "Entrez Gene: CAPZB capping protein (actin filament) muscle Z-line, beta".
  2. ↑ Schafer DA, Korshunova YO, Schroer TA, Cooper JA (October 1994). "Differential localization and sequence analysis of capping protein beta-subunit isoforms of vertebrates". The Journal of Cell Biology. 127 (2): 453–65. doi:10.1083/jcb.127.2.453. PMC 2120197. PMID 7929588.
  3. ↑ 3.0 3.1 von Bülow M, Rackwitz HR, Zimbelmann R, Franke WW (May 1997). "CP beta3, a novel isoform of an actin-binding protein, is a component of the cytoskeletal calyx of the mammalian sperm head". Experimental Cell Research. 233 (1): 216–24. doi:10.1006/excr.1997.3564. PMID 9184090.
  4. ↑ "F-actin-capping protein subunit beta". COPaKB.
  5. ↑ Zong NC, Li H, Li H, Lam MP, Jimenez RC, Kim CS, Deng N, Kim AK, Choi JH, Zelaya I, Liem D, Meyer D, Odeberg J, Fang C, Lu HJ, Xu T, Weiss J, Duan H, Uhlen M, Yates JR, Apweiler R, Ge J, Hermjakob H, Ping P (October 2013). "Integration of cardiac proteome biology and medicine by a specialized knowledgebase". Circulation Research. 113 (9): 1043–53. doi:10.1161/CIRCRESAHA.113.301151. PMC 4076475. PMID 23965338.
  6. ↑ Hart MC, Korshunova YO, Cooper JA (1997). "Vertebrates have conserved capping protein alpha isoforms with specific expression patterns". Cell Motility and the Cytoskeleton. 38 (2): 120–32. doi:10.1002/(SICI)1097-0169(1997)38:2<120::AID-CM2>3.0.CO;2-B. PMID 9331217.
  7. ↑ Casella JF, Craig SW, Maack DJ, Brown AE (July 1987). "Cap Z(36/32), a barbed end actin-capping protein, is a component of the Z-line of skeletal muscle". The Journal of Cell Biology. 105 (1): 371–9. doi:10.1083/jcb.105.1.371. PMC 2114938. PMID 3301868.
  8. ↑ 8.0 8.1 Hishiya A, Kitazawa T, Takayama S (November 2010). "BAG3 and Hsc70 interact with actin capping protein CapZ to maintain myofibrillar integrity under mechanical stress". Circulation Research. 107 (10): 1220–31. doi:10.1161/CIRCRESAHA.110.225649. PMC 2980587. PMID 20884878.
  9. ↑ Schafer DA, Hug C, Cooper JA (January 1995). "Inhibition of CapZ during myofibrillogenesis alters assembly of actin filaments". The Journal of Cell Biology. 128 (1–2): 61–70. doi:10.1083/jcb.128.1.61. PMC 2120327. PMID 7822423.
  10. ↑ Papa I, Astier C, Kwiatek O, Raynaud F, Bonnal C, Lebart MC, Roustan C, Benyamin Y (February 1999). "Alpha actinin-CapZ, an anchoring complex for thin filaments in Z-line". Journal of Muscle Research and Cell Motility. 20 (2): 187–97. doi:10.1023/A:1005489319058. PMID 10412090.
  11. ↑ 11.0 11.1 Hart MC, Cooper JA (December 1999). "Vertebrate isoforms of actin capping protein beta have distinct functions In vivo". The Journal of Cell Biology. 147 (6): 1287–98. doi:10.1083/jcb.147.6.1287. PMC 2168092. PMID 10601341.
  12. ↑ Pyle WG, Hart MC, Cooper JA, Sumandea MP, de Tombe PP, Solaro RJ (June 2002). "Actin capping protein: an essential element in protein kinase signaling to the myofilaments". Circulation Research. 90 (12): 1299–306. doi:10.1161/01.res.0000024389.03152.22. PMID 12089068.
  13. ↑ Yang FH, Pyle WG (March 2012). "Reduced cardiac CapZ protein protects hearts against acute ischemia-reperfusion injury and enhances preconditioning". Journal of Molecular and Cellular Cardiology. 52 (3): 761–72. doi:10.1016/j.yjmcc.2011.11.013. PMID 22155006.
  14. ↑ "Anxiety data for Capzb". Wellcome Trust Sanger Institute.
  15. ↑ "Clinical chemistry data for Capzb". Wellcome Trust Sanger Institute.
  16. ↑ "Salmonella infection data for Capzb". Wellcome Trust Sanger Institute.
  17. ↑ "Citrobacter infection data for Capzb". Wellcome Trust Sanger Institute.
  18. ↑ 18.0 18.1 18.2 18.3 Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica. 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x.
  19. ↑ Mouse Resources Portal, Wellcome Trust Sanger Institute.
  20. ↑ "International Knockout Mouse Consortium".
  21. ↑ "Mouse Genome Informatics".
  22. ↑ Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (June 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–42. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
  23. ↑ Dolgin E (June 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
  24. ↑ Collins FS, Rossant J, Wurst W (January 2007). "A mouse for all reasons". Cell. 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247.
  25. ↑ van der Weyden L, White JK, Adams DJ, Logan DW (June 2011). "The mouse genetics toolkit: revealing function and mechanism". Genome Biology. 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353.

Further reading

  • Barron-Casella EA, Torres MA, Scherer SW, Heng HH, Tsui LC, Casella JF (September 1995). "Sequence analysis and chromosomal localization of human Cap Z. Conserved residues within the actin-binding domain may link Cap Z to gelsolin/severin and profilin protein families". The Journal of Biological Chemistry. 270 (37): 21472–9. doi:10.1074/jbc.270.37.21472. PMID 7665558.
  • Gevaert K, Goethals M, Martens L, Van Damme J, Staes A, Thomas GR, Vandekerckhove J (May 2003). "Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides". Nature Biotechnology. 21 (5): 566–9. doi:10.1038/nbt810. PMID 12665801.
  • Bouwmeester T, Bauch A, Ruffner H, Angrand PO, Bergamini G, Croughton K, Cruciat C, Eberhard D, Gagneur J, Ghidelli S, Hopf C, Huhse B, Mangano R, Michon AM, Schirle M, Schlegl J, Schwab M, Stein MA, Bauer A, Casari G, Drewes G, Gavin AC, Jackson DB, Joberty G, Neubauer G, Rick J, Kuster B, Superti-Furga G (February 2004). "A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway". Nature Cell Biology. 6 (2): 97–105. doi:10.1038/ncb1086. PMID 14743216.
  • Bruneel A, Labas V, Mailloux A, Sharma S, Royer N, Vinh J, Pernet P, Vaubourdolle M, Baudin B (October 2005). "Proteomics of human umbilical vein endothelial cells applied to etoposide-induced apoptosis". Proteomics. 5 (15): 3876–84. doi:10.1002/pmic.200401239. PMID 16130169.
  • Stelzl U, Worm U, Lalowski M, Haenig C, Brembeck FH, Goehler H, Stroedicke M, Zenkner M, Schoenherr A, Koeppen S, Timm J, Mintzlaff S, Abraham C, Bock N, Kietzmann S, Goedde A, Toksöz E, Droege A, Krobitsch S, Korn B, Birchmeier W, Lehrach H, Wanker EE (September 2005). "A human protein-protein interaction network: a resource for annotating the proteome". Cell. 122 (6): 957–68. doi:10.1016/j.cell.2005.08.029. PMID 16169070.
  • Wells CD, Fawcett JP, Traweger A, Yamanaka Y, Goudreault M, Elder K, Kulkarni S, Gish G, Virag C, Lim C, Colwill K, Starostine A, Metalnikov P, Pawson T (May 2006). "A Rich1/Amot complex regulates the Cdc42 GTPase and apical-polarity proteins in epithelial cells". Cell. 125 (3): 535–48. doi:10.1016/j.cell.2006.02.045. PMID 16678097.
  • Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, McBroom-Cerajewski L, Robinson MD, O'Connor L, Li M, Taylor R, Dharsee M, Ho Y, Heilbut A, Moore L, Zhang S, Ornatsky O, Bukhman YV, Ethier M, Sheng Y, Vasilescu J, Abu-Farha M, Lambert JP, Duewel HS, Stewart II, Kuehl B, Hogue K, Colwill K, Gladwish K, Muskat B, Kinach R, Adams SL, Moran MF, Morin GB, Topaloglou T, Figeys D (2007). "Large-scale mapping of human protein-protein interactions by mass spectrometry". Molecular Systems Biology. 3 (1): 89. doi:10.1038/msb4100134. PMC 1847948. PMID 17353931.

External links

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