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Gene Review

Actn1  -  actinin, alpha 1

Mus musculus

Synonyms: 3110023F10Rik, Actn1a, Alpha-actinin cytoskeletal isoform, Alpha-actinin-1, F-actin cross-linking protein, ...
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Disease relevance of Actn1

  • Calcineurin, which binds to the Z-disc in cardiomyocytes via alpha-actinin, promotes cardiac hypertrophy in response to numerous pathologic stimuli [1].
  • We previously had shown that anti-DNA Abs that cross-react with alpha-actinin may be important in the pathogenesis of murine and human lupus nephritis; in murine models, we had found that a significant proportion of pathogenic serum and kidney-deposited Igs are alpha-actinin reactive [2].
  • We conclude that enhanced alpha-actinin expression may determine the extent of Ig deposition in the Ab-mediated kidney disease in lupus [2].
  • Thymic B lymphocyte clones from patients with myasthenia gravis secrete monoclonal striational autoantibodies reacting with myosin, alpha actinin, or actin [3].
  • When a stab wound was made in brain, F-actin and alpha-actinin were upregulated in reactive astrocytes [4].

High impact information on Actn1

  • These contractions leave periodic rows of matrix bound beta3-integrin and paxillin while generating waves of rearward moving actin bound alpha-actinin and MLCK [5].
  • This analysis also showed for the first time the coexistence and alpha and beta tubulin, vimentin, alpha actinin and three other polypeptides present in intermediate-filament-enriched cytoplast cytoskeletons (spots 12, 24 and 31) [6].
  • The participation of alpha-actinin in the capping of cell membrane components [7].
  • The enrichment of alpha-actinin under the clustered surface molecules was already apparent in early stages (patching) of the capping process, with or without 10 mM sodium azide present [7].
  • Prolonged incubation of the cells with the different ligands resulted in endocytosis of the ligand-receptor complex. alpha-Actinin was not associated with the inernalized complex, however, suggesting that it may dissociate from the patched or capped surface structures at some stage during endocytosis [7].

Biological context of Actn1


Anatomical context of Actn1


Associations of Actn1 with chemical compounds

  • The levels of PIP2 bound to alpha-actinin decrease in response to platelet-derived growth factor (PDGF) [9].
  • Association of alpha-actinin with clustered integrin is therefore not sufficient to induce the co-localization of F-actin [17].
  • During the same time interval, alpha-actinin is mobilized to the cell periphery at cell "ruffles." However, 12(S)-HETE showed little or no effects on actin-binding proteins filamin and tropomyosin or on microtubules [18].
  • During recovery, which was initiated by removing NaN3 and 2-deoxyglucose from the medium, lamellipodia appeared rapidly and alpha-actinin dispersed from contracted aggregates [19].
  • The critical lysine residue localizes within a short alpha-helix, raising the possibility that mutagenesis-induced alterations in alpha-actinin-binding capacity might be attributed to the disruption of a key structural element [11].

Physical interactions of Actn1

  • Nonphosphorylated and Thr(286)-autophosphorylated CaMKII bind to alpha-actinin with similar efficacy, but autophosphorylation at Thr(305/306) or Ca(2+)/calmodulin binding significantly reduce this binding [20].

Enzymatic interactions of Actn1

  • The protein appears to be located in focal contacts where it codistributes with beta 1 integrins. pp120 is distinct from the beta 1 subunit of integrins and from vinculin and alpha-actinin. pp120 is rapidly dephosphorylated in cells suspended by trypsinization but becomes rapidly phosphorylated in cells attaching and spreading on fibronectin [21].

Co-localisations of Actn1

  • Analysis of both wild-type and desmin-null fibers revealed that the costamere protein talin colocalized with the Z-disk protein alpha-actinin, even at very high strains and stresses [22].
  • During myofibril assembly in cultured chick cardiomyocytes, N-RAP and filamin appear to co-localize with alpha-actinin in the earliest myofibril precursors found near the cell periphery, as well as in the nascent myofibrils that form as these structures fuse laterally [23].
  • PKC-epsilon-GFP bound with a striated pattern that co-localized with alpha-actinin, a marker of the Z-line of the sarcomere [24].

Regulatory relationships of Actn1


Other interactions of Actn1

  • Alp also colocalizes at the intercalated disc with alpha-actinin and gamma-catenin, the latter being a known disease gene for human RV dysplasia [13].
  • At the subcellular level in later embryonic and postnatal mouse cardiomyocytes, Scn1b was present in T-tubules as identified by immunostaining of alpha-actinin, and in the intercalated disks as identified by immunostaining of connexin 43 [26].
  • Western blot analysis demonstrated decreased concentrations of z-disk proteins alpha-actinin and plectin and membrane scaffolding proteins dystrophin and beta-spectrin in muscle exposed to lengthening contractions compared with contralateral control muscle [27].
  • The beating cells of both groups, stained positive with anti alpha-actinin, desmin, cardiac troponin I and connexin antibodies, and revealed similar ultrastructural features [28].
  • In vitro studies demonstrated that individual domains within Cypher localize independently to the Z-line via interactions with alpha-actinin or other Z-line components [29].

Analytical, diagnostic and therapeutic context of Actn1


  1. Atrogin-1/muscle atrophy F-box inhibits calcineurin-dependent cardiac hypertrophy by participating in an SCF ubiquitin ligase complex. Li, H.H., Kedar, V., Zhang, C., McDonough, H., Arya, R., Wang, D.Z., Patterson, C. J. Clin. Invest. (2004) [Pubmed]
  2. Differential binding of cross-reactive anti-DNA antibodies to mesangial cells: the role of alpha-actinin. Zhao, Z., Deocharan, B., Scherer, P.E., Ozelius, L.J., Putterman, C. J. Immunol. (2006) [Pubmed]
  3. Thymic B lymphocyte clones from patients with myasthenia gravis secrete monoclonal striational autoantibodies reacting with myosin, alpha actinin, or actin. Williams, C.L., Lennon, V.A. J. Exp. Med. (1986) [Pubmed]
  4. Upregulation of F-actin and alpha-actinin in reactive astrocytes. Abd-El-Basset, E.M., Fedoroff, S. J. Neurosci. Res. (1997) [Pubmed]
  5. Periodic lamellipodial contractions correlate with rearward actin waves. Giannone, G., Dubin-Thaler, B.J., Döbereiner, H.G., Kieffer, N., Bresnick, A.R., Sheetz, M.P. Cell (2004) [Pubmed]
  6. Coexistence of three major isoactins in a single sarcoma 180 cell. Bravo, R., Fey, S.J., Small, J.V., Larsen, P.M., Celis, J.E. Cell (1981) [Pubmed]
  7. The participation of alpha-actinin in the capping of cell membrane components. Geiger, B., Singer, S.J. Cell (1979) [Pubmed]
  8. Differences in elasticity of vinculin-deficient F9 cells measured by magnetometry and atomic force microscopy. Goldmann, W.H., Galneder, R., Ludwig, M., Xu, W., Adamson, E.D., Wang, N., Ezzell, R.M. Exp. Cell Res. (1998) [Pubmed]
  9. alpha-Actinin and vinculin are PIP2-binding proteins involved in signaling by tyrosine kinase. Fukami, K., Endo, T., Imamura, M., Takenawa, T. J. Biol. Chem. (1994) [Pubmed]
  10. N terminus is essential for tropomyosin functions: N-terminal modification disrupts stress fiber organization and abolishes anti-oncogenic effects of tropomyosin-1. Bharadwaj, S., Hitchcock-DeGregori, S., Thorburn, A., Prasad, G.L. J. Biol. Chem. (2004) [Pubmed]
  11. Fine mapping of the alpha-actinin binding site within cysteine-rich protein. Harper, B.D., Beckerle, M.C., Pomiès, P. Biochem. J. (2000) [Pubmed]
  12. Targeted disruption of N-RAP gene function by RNA interference: a role for N-RAP in myofibril organization. Dhume, A., Lu, S., Horowits, R. Cell Motil. Cytoskeleton (2006) [Pubmed]
  13. Adult mice deficient in actinin-associated LIM-domain protein reveal a developmental pathway for right ventricular cardiomyopathy. Pashmforoush, M., Pomiès, P., Peterson, K.L., Kubalak, S., Ross, J., Hefti, A., Aebi, U., Beckerle, M.C., Chien, K.R. Nat. Med. (2001) [Pubmed]
  14. Integrin-mediated cell adhesion: the cytoskeletal connection. Critchley, D.R., Holt, M.R., Barry, S.T., Priddle, H., Hemmings, L., Norman, J. Biochem. Soc. Symp. (1999) [Pubmed]
  15. Plakoglobin is a component of the filamentous subplasmalemmal coat of lens cells. Franke, W.W., Kapprell, H.P., Cowin, P. Eur. J. Cell Biol. (1987) [Pubmed]
  16. Extensive but coordinated reorganization of the membrane skeleton in myofibers of dystrophic (mdx) mice. Williams, M.W., Bloch, R.J. J. Cell Biol. (1999) [Pubmed]
  17. Mapping in vivo associations of cytoplasmic proteins with integrin beta 1 cytoplasmic domain mutants. Lewis, J.M., Schwartz, M.A. Mol. Biol. Cell (1995) [Pubmed]
  18. The lipoxygenase metabolite, 12(S)-HETE, induces a protein kinase C-dependent cytoskeletal rearrangement and retraction of microvascular endothelial cells. Tang, D.G., Timar, J., Grossi, I.M., Renaud, C., Kimler, V.A., Diglio, C.A., Taylor, J.D., Honn, K.V. Exp. Cell Res. (1993) [Pubmed]
  19. Reorganization of alpha-actinin and vinculin in living cells following ATP depletion and replenishment. Wang, Y.L. Exp. Cell Res. (1986) [Pubmed]
  20. Differential modulation of Ca2+/calmodulin-dependent protein kinase II activity by regulated interactions with N-methyl-D-aspartate receptor NR2B subunits and alpha-actinin. Robison, A.J., Bartlett, R.K., Bass, M.A., Colbran, R.J. J. Biol. Chem. (2005) [Pubmed]
  21. Fibronectin/integrin interaction induces tyrosine phosphorylation of a 120-kDa protein. Guan, J.L., Trevithick, J.E., Hynes, R.O. Cell Regul. (1991) [Pubmed]
  22. Structural and functional roles of desmin in mouse skeletal muscle during passive deformation. Shah, S.B., Davis, J., Weisleder, N., Kostavassili, I., McCulloch, A.D., Ralston, E., Capetanaki, Y., Lieber, R.L. Biophys. J. (2004) [Pubmed]
  23. New N-RAP-binding partners alpha-actinin, filamin and Krp1 detected by yeast two-hybrid screening: implications for myofibril assembly. Lu, S., Carroll, S.L., Herrera, A.H., Ozanne, B., Horowits, R. J. Cell. Sci. (2003) [Pubmed]
  24. Localization and kinetics of protein kinase C-epsilon anchoring in cardiac myocytes. Robia, S.L., Ghanta, J., Robu, V.G., Walker, J.W. Biophys. J. (2001) [Pubmed]
  25. Synaptopodin regulates the actin-bundling activity of alpha-actinin in an isoform-specific manner. Asanuma, K., Kim, K., Oh, J., Giardino, L., Chabanis, S., Faul, C., Reiser, J., Mundel, P. J. Clin. Invest. (2005) [Pubmed]
  26. Temporal and spatial expression pattern of beta1 sodium channel subunit during heart development. Domínguez, J.N., Navarro, F., Franco, D., Thompson, R.P., Aránega, A.E. Cardiovasc. Res. (2005) [Pubmed]
  27. Cytoskeletal disruption and small heat shock protein translocation immediately after lengthening contractions. Koh, T.J., Escobedo, J. Am. J. Physiol., Cell Physiol. (2004) [Pubmed]
  28. Effects of oxytocin on cardiomyocyte differentiation from mouse embryonic stem cells. Hatami, L., Valojerdi, M.R., Mowla, S.J. Int. J. Cardiol. (2007) [Pubmed]
  29. Ablation of Cypher, a PDZ-LIM domain Z-line protein, causes a severe form of congenital myopathy. Zhou, Q., Chu, P.H., Huang, C., Cheng, C.F., Martone, M.E., Knoll, G., Shelton, G.D., Evans, S., Chen, J. J. Cell Biol. (2001) [Pubmed]
  30. Organization of stress fibers in cultured fibroblasts after extraction of actin with bovine brain gelsolin-like protein. Verkhovsky, A.B., Surgucheva, I.G., Svitkina, T.M., Tint, I.S., Gelfand, V.I. Exp. Cell Res. (1987) [Pubmed]
  31. Relation of retinomotor responses and contractile proteins in vertebrate retinas. Drenckhahn, D., Wagner, H.J. Eur. J. Cell Biol. (1985) [Pubmed]
  32. Myofibril degeneration caused by tropomodulin overexpression leads to dilated cardiomyopathy in juvenile mice. Sussman, M.A., Welch, S., Cambon, N., Klevitsky, R., Hewett, T.E., Price, R., Witt, S.A., Kimball, T.R. J. Clin. Invest. (1998) [Pubmed]
  33. Lymphocyte alpha-actinin. Relationship to cell membrane and co-capping with surface receptors. Hoessli, D., Rungger-Brändle, E., Jockusch, B.M., Gabbiani, G. J. Cell Biol. (1980) [Pubmed]
  34. Two mammalian heat shock proteins, HSP90 and HSP100, are actin-binding proteins. Koyasu, S., Nishida, E., Kadowaki, T., Matsuzaki, F., Iida, K., Harada, F., Kasuga, M., Sakai, H., Yahara, I. Proc. Natl. Acad. Sci. U.S.A. (1986) [Pubmed]
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