Actin, alpha skeletal muscle explained

Actin, alpha skeletal muscle is a protein that in humans is encoded by the ACTA1 gene.^{[1] [2]}

Actin alpha 1 which is expressed in skeletal muscle is one of six different actin isoforms which have been identified. Actins are highly conserved proteins that are involved in cell motility, structure and integrity. Alpha actins are a major constituent of the contractile apparatus.^[3]

Skeletal actin gene expression

Skeletal alpha actin expression is induced by stimuli and conditions known to cause muscle formation.^[4] Such conditions result in fusion of committed cells (satellite cells) into myotubes, to form muscle fibers. Skeletal actin itself, when expressed, causes expression of several other "myogenic genes", which are essential to muscle formation.^[5] One key transcription factor that activates skeletal actin gene expression is Serum Response Factor ("SRF"), a protein that binds to specific sites on the promoter DNA of the actin gene.^[6] SRF may bring a number of other proteins to the promoter of skeletal actin, such as androgen receptor, and thereby contribute to induction of skeletal actin gene expression by androgenic (often termed "anabolic") steroids.^[7]

Interactions

Actin, alpha 1 has been shown to interact with TMSB4X,^{[8] [9]} MIB2^[10] and PRKCE.^[11]

Clinical significance

Mutations in the ACTA1 gene are known to cause the following conditions:^[12]

• Nemaline myopathy 3 (NEM3);
• Myopathy, actin, congenital, with excess of thin myofilaments (MPCETM);
• Myopathy, congenital, with fiber-type disproportion (CFTD);
• Myopathy, scapulohumeroperoneal (SHPM).

See also

• Actin
• ACTB

Further reading

• Snásel J, Pichová I . The cleavage of host cell proteins by HIV-1 protease . Folia Biologica . 42 . 5 . 227–30 . 1997 . 8997639 . 10.1007/BF02818986 . 7617882 .
• Di Fiore PP, Scita G . Eps8 in the midst of GTPases . The International Journal of Biochemistry & Cell Biology . 34 . 10 . 1178–83 . October 2002 . 12127568 . 10.1016/S1357-2725(02)00064-X .
• Ogawa H, Shiraki H, Matsuda Y, Nakagawa H . Interaction of adenylosuccinate synthetase with F-actin . European Journal of Biochemistry . 85 . 2 . 331–7 . April 1978 . 648524 . 10.1111/j.1432-1033.1978.tb12243.x . free .
• den Hartigh JC, van Bergen en Henegouwen PM, Verkleij AJ, Boonstra J . The EGF receptor is an actin-binding protein . The Journal of Cell Biology . 119 . 2 . 349–55 . October 1992 . 1383230 . 2289650 . 10.1083/jcb.119.2.349 .
• Adams LD, Tomasselli AG, Robbins P, Moss B, Heinrikson RL . HIV-1 protease cleaves actin during acute infection of human T-lymphocytes . AIDS Research and Human Retroviruses . 8 . 2 . 291–5 . February 1992 . 1540415 . 10.1089/aid.1992.8.291 .
• Levine BA, Moir AJ, Patchell VB, Perry SV . Binding sites involved in the interaction of actin with the N-terminal region of dystrophin . FEBS Letters . 298 . 1 . 44–8 . February 1992 . 1544421 . 10.1016/0014-5793(92)80019-D . free .
• Rijken PJ, Hage WJ, van Bergen en Henegouwen PM, Verkleij AJ, Boonstra J . Epidermal growth factor induces rapid reorganization of the actin microfilament system in human A431 cells . Journal of Cell Science . 100 (Pt 3) . 3 . 491–9 . November 1991 . 10.1242/jcs.100.3.491 . 1808202 . free .
• Tomasselli AG, Hui JO, Adams L, Chosay J, Lowery D, Greenberg B, Yem A, Deibel MR, Zürcher-Neely H, Heinrikson RL . Actin, troponin C, Alzheimer amyloid precursor protein and pro-interleukin 1 beta as substrates of the protease from human immunodeficiency virus . The Journal of Biological Chemistry . 266 . 22 . 14548–53 . August 1991 . 10.1016/S0021-9258(18)98721-1 . 1907279 . free .
• Shoeman RL, Kesselmier C, Mothes E, Höner B, Traub P . Non-viral cellular substrates for human immunodeficiency virus type 1 protease . FEBS Letters . 278 . 2 . 199–203 . January 1991 . 1991513 . 10.1016/0014-5793(91)80116-K . free .
• Winder SJ, Walsh MP . Smooth muscle calponin. Inhibition of actomyosin MgATPase and regulation by phosphorylation . The Journal of Biological Chemistry . 265 . 17 . 10148–55 . June 1990 . 10.1016/S0021-9258(19)38792-7 . 2161834 . free .
• Kabsch W, Mannherz HG, Suck D, Pai EF, Holmes KC . Atomic structure of the actin:DNase I complex . Nature . 347 . 6288 . 37–44 . September 1990 . 2395459 . 10.1038/347037a0 . 1990Natur.347...37K . 925337 .
• Takahashi K, Hiwada K, Kokubu T . Vascular smooth muscle calponin. A novel troponin T-like protein . Hypertension . 11 . 6 Pt 2 . 620–6 . June 1988 . 2455687 . 10.1161/01.hyp.11.6.620 . free .
• Taylor A, Erba HP, Muscat GE, Kedes L . Nucleotide sequence and expression of the human skeletal alpha-actin gene: evolution of functional regulatory domains . Genomics . 3 . 4 . 323–36 . November 1988 . 2907503 . 10.1016/0888-7543(88)90123-1 .
• Shen BW, Josephs R, Steck TL . Ultrastructure of the intact skeleton of the human erythrocyte membrane . The Journal of Cell Biology . 102 . 3 . 997–1006 . March 1986 . 2936753 . 2114132 . 10.1083/jcb.102.3.997 .
• Burgess DR, Broschat KO, Hayden JM . Tropomyosin distinguishes between the two actin-binding sites of villin and affects actin-binding properties of other brush border proteins . The Journal of Cell Biology . 104 . 1 . 29–40 . January 1987 . 3793760 . 2117036 . 10.1083/jcb.104.1.29 .
• Kedes L, Ng SY, Lin CS, Gunning P, Eddy R, Shows T, Leavitt J . The human beta-actin multigene family . Transactions of the Association of American Physicians . 98 . 42–6 . 1986 . 3842206 .
• Hanauer A, Levin M, Heilig R, Daegelen D, Kahn A, Mandel JL . Isolation and characterization of cDNA clones for human skeletal muscle alpha actin . Nucleic Acids Research . 11 . 11 . 3503–16 . June 1983 . 6190133 . 325982 . 10.1093/nar/11.11.3503 .
• Bretscher A, Weber K . Villin is a major protein of the microvillus cytoskeleton which binds both G and F actin in a calcium-dependent manner . Cell . 20 . 3 . 839–47 . July 1980 . 6893424 . 10.1016/0092-8674(80)90330-X . 568395 .

External links

• GeneReviews/NCBI/NIH/UW entry on Nemaline Myopathy

Notes and References

1. Mogensen J, Kruse TA, Børglum AD . Assignment of the human skeletal muscle [FC12]a-actin gene (ACTA1) to chromosome 1q42.13→q42.2 by radiation hybrid mapping . Cytogenetics and Cell Genetics . 83 . 3–4 . 224–5 . March 1999 . 10072583 . 10.1159/000015184 . 84202330 .
2. Gunning P, Ponte P, Okayama H, Engel J, Blau H, Kedes L . Isolation and characterization of full-length cDNA clones for human alpha-, beta-, and gamma-actin mRNAs: skeletal but not cytoplasmic actins have an amino-terminal cysteine that is subsequently removed . Molecular and Cellular Biology . 3 . 5 . 787–95 . May 1983 . 6865942 . 368601 . 10.1128/mcb.3.5.787 .
3. Web site: Entrez Gene: ACTA1 actin, alpha 1, skeletal muscle.
4. Bandman E . Contractile protein isoforms in muscle development . Developmental Biology . 154 . 2 . 273–83 . December 1992 . 1358730 . 10.1016/0012-1606(92)90067-Q .
5. Gunning PW, Ferguson V, Brennan KJ, Hardeman EC . Alpha-skeletal actin induces a subset of muscle genes independently of muscle differentiation and withdrawal from the cell cycle . Journal of Cell Science . 114 . Pt 3 . 513–24 . February 2001 . 10.1242/jcs.114.3.513 . 11171321 .
6. Belaguli NS, Zhou W, Trinh TH, Majesky MW, Schwartz RJ . Dominant negative murine serum response factor: alternative splicing within the activation domain inhibits transactivation of serum response factor binding targets . Molecular and Cellular Biology . 19 . 7 . 4582–91 . July 1999 . 10373507 . 84256 . 10.1128/mcb.19.7.4582 .
7. Vlahopoulos S, Zimmer WE, Jenster G, Belaguli NS, Balk SP, Brinkmann AO, Lanz RB, Zoumpourlis VC, Schwartz RJ . Recruitment of the androgen receptor via serum response factor facilitates expression of a myogenic gene . The Journal of Biological Chemistry . 280 . 9 . 7786–92 . March 2005 . 15623502 . 10.1074/jbc.M413992200 . free .
8. Ballweber E, Hannappel E, Huff T, Stephan H, Haener M, Taschner N, Stoffler D, Aebi U, Mannherz HG . Polymerisation of chemically cross-linked actin:thymosin beta(4) complex to filamentous actin: alteration in helical parameters and visualisation of thymosin beta(4) binding on F-actin . Journal of Molecular Biology . 315 . 4 . 613–25 . January 2002 . 11812134 . 10.1006/jmbi.2001.5281 .
9. Safer D, Sosnick TR, Elzinga M . Thymosin beta 4 binds actin in an extended conformation and contacts both the barbed and pointed ends . Biochemistry . 36 . 19 . 5806–16 . May 1997 . 9153421 . 10.1021/bi970185v .
10. Takeuchi T, Heng HH, Ye CJ, Liang SB, Iwata J, Sonobe H, Ohtsuki Y . Down-regulation of a novel actin-binding molecule, skeletrophin, in malignant melanoma . The American Journal of Pathology . 163 . 4 . 1395–404 . October 2003 . 14507647 . 1868282 . 10.1016/S0002-9440(10)63497-9 .
11. England K, Ashford D, Kidd D, Rumsby M . PKC epsilon is associated with myosin IIA and actin in fibroblasts . Cellular Signalling . 14 . 6 . 529–36 . June 2002 . 11897493 . 10.1016/S0898-6568(01)00277-7 .
12. Web site: UniProt . 2023-09-09 . www.uniprot.org.