CAPZB explained

F-actin-capping protein subunit beta, also known as CapZβ, is a protein that in humans is encoded by the CAPZB gene. 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.^{[1] [2]} 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. 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. CapZ interacts with α-actinin, nebulette, nebulin, HSC70. 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.

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. Isoforms of the CapZβ (β1 and β2) have distinct functions, as CapZβ1 anchors actin at Z-discs and CapZβ2 at intercalated discs. 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.^[4] 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.^[5] A later study showed that partial reduction of CapZβ was cardioprotective during ischemia-reperfusion injury, concomitant with altered PKC isoform translocation to myofilaments.^[6] 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.

Clinical Significance

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

Further reading

• Barron-Casella EA, Torres MA, Scherer SW, Heng HH, Tsui LC, Casella JF . 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 . September 1995 . 7665558 . 10.1074/jbc.270.37.21472 . free .
• Gevaert K, Goethals M, Martens L, Van Damme J, Staes A, Thomas GR, Vandekerckhove J . Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides . Nature Biotechnology . 21 . 5 . 566–9 . May 2003 . 12665801 . 10.1038/nbt810 . 23783563 .
• 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 . A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway . Nature Cell Biology . 6 . 2 . 97–105 . February 2004 . 14743216 . 10.1038/ncb1086 . 11683986 .
• Bruneel A, Labas V, Mailloux A, Sharma S, Royer N, Vinh J, Pernet P, Vaubourdolle M, Baudin B . Proteomics of human umbilical vein endothelial cells applied to etoposide-induced apoptosis . Proteomics . 5 . 15 . 3876–84 . October 2005 . 16130169 . 10.1002/pmic.200401239 . 26007149 .
• 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 . A human protein-protein interaction network: a resource for annotating the proteome . Cell . 122 . 6 . 957–68 . September 2005 . 16169070 . 10.1016/j.cell.2005.08.029 . 11858/00-001M-0000-0010-8592-0 . 8235923 . free .
• 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 . A Rich1/Amot complex regulates the Cdc42 GTPase and apical-polarity proteins in epithelial cells . Cell . 125 . 3 . 535–48 . May 2006 . 16678097 . 10.1016/j.cell.2006.02.045 . 18651810 . free .
• 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 . Large-scale mapping of human protein-protein interactions by mass spectrometry . Molecular Systems Biology . 3 . 1 . 89 . 2007 . 17353931 . 1847948 . 10.1038/msb4100134 .

External links

• Mass spectrometry characterization of human CAPZB at COPaKB

Notes and References

1. Web site: F-actin-capping protein subunit beta . COPaKB .
2. 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 . Integration of cardiac proteome biology and medicine by a specialized knowledgebase . Circulation Research . 113 . 9 . 1043–53 . October 2013 . 23965338 . 4076475 . 10.1161/CIRCRESAHA.113.301151 .
3. von Bülow M, Rackwitz HR, Zimbelmann R, Franke WW . 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 . May 1997 . 9184090 . 10.1006/excr.1997.3564 .
4. Hart MC, Cooper JA . Vertebrate isoforms of actin capping protein beta have distinct functions In vivo . The Journal of Cell Biology . 147 . 6 . 1287–98 . December 1999 . 10601341 . 10.1083/jcb.147.6.1287 . 2168092.
5. Pyle WG, Hart MC, Cooper JA, Sumandea MP, de Tombe PP, Solaro RJ . Actin capping protein: an essential element in protein kinase signaling to the myofilaments . Circulation Research . 90 . 12 . 1299–306 . June 2002 . 12089068 . 10.1161/01.res.0000024389.03152.22 . free .
6. Yang FH, Pyle WG . Reduced cardiac CapZ protein protects hearts against acute ischemia-reperfusion injury and enhances preconditioning . Journal of Molecular and Cellular Cardiology . 52 . 3 . 761–72 . March 2012 . 22155006 . 10.1016/j.yjmcc.2011.11.013 .