Gene Symbol: Actn4
Description: actinin alpha 4
Alias: alpha-actinin-4, F-actin cross-linking protein, non-muscle alpha-actinin 4
Species: rat
Products:     Actn4

Top Publications

  1. Daniliuc S, Bitterman H, Rahat M, Kinarty A, Rosenzweig D, Lahat N, et al. Hypoxia inactivates inducible nitric oxide synthase in mouse macrophages by disrupting its interaction with alpha-actinin 4. J Immunol. 2003;171:3225-32 pubmed
    ..We suggest that the intracellular localization and interactions of iNOS with the cytoskeleton are crucial for its activity, and that hypoxia inactivates iNOS by disrupting these interactions. ..
  2. Ziane R, Huang H, Moghadaszadeh B, Beggs A, Levesque G, Chahine M. Cell membrane expression of cardiac sodium channel Na(v)1.5 is modulated by alpha-actinin-2 interaction. Biochemistry. 2010;49:166-78 pubmed publisher
    ..Our data suggest that alpha-actinin-2, which is known to regulate the functional expression of the potassium channels, may play a role in anchoring Na(v)1.5 to the membrane by connecting the channel to the actin cytoskeleton network. ..
  3. Sanchez Ponce D, Blazquez Llorca L, DeFelipe J, Garrido J, Munoz A. Colocalization of ?-actinin and synaptopodin in the pyramidal cell axon initial segment. Cereb Cortex. 2012;22:1648-61 pubmed publisher
    ..Together, these results indicate that ?-actinin and the actin cytoskeleton are important components of the cisternal organelle that are probably required to stabilize the AIS. ..
  4. Araki N, Hatae T, Yamada T, Hirohashi S. Actinin-4 is preferentially involved in circular ruffling and macropinocytosis in mouse macrophages: analysis by fluorescence ratio imaging. J Cell Sci. 2000;113 ( Pt 18):3329-40 pubmed
    ..A similar redistribution of actinin-4 was also observed during phagocytosis, suggesting that actinin-4 may play the same role in the two mechanistically analogous types of endocytosis, i.e. macropinocytosis and phagocytosis. ..
  5. Zhao X, Hsu K, Lim J, Bruggeman L, Kao H. α-Actinin 4 potentiates nuclear factor κ-light-chain-enhancer of activated B-cell (NF-κB) activity in podocytes independent of its cytoplasmic actin binding function. J Biol Chem. 2015;290:338-49 pubmed publisher
    ..Mutations in the actin-binding protein, α-actinin 4 (ACTN4), are linked to focal segmental glomerulosclerosis (FSGS), a chronic kidney disease characterized by proteinuria...
  6. Khurana S, Chakraborty S, Lam M, Liu Y, Su Y, Zhao X, et al. Familial focal segmental glomerulosclerosis (FSGS)-linked ?-actinin 4 (ACTN4) protein mutants lose ability to activate transcription by nuclear hormone receptors. J Biol Chem. 2012;287:12027-35 pubmed publisher
    Mutations in ?-actinin 4 (ACTN4) are linked to familial forms of focal segmental glomerulosclerosis (FSGS), a kidney disease characterized by proteinuria due to podocyte injury...
  7. El Husseini A, Kwasnicka D, Yamada T, Hirohashi S, Vincent S. BERP, a novel ring finger protein, binds to alpha-actinin-4. Biochem Biophys Res Commun. 2000;267:906-11 pubmed
    ..These proteins could also be colocalized immunohistochemically in the cytoplasm of differentiated PC12 cells. We suggest that BERP may anchor class V myosins to particular cell domains via its interaction with alpha-actinin-4. ..
  8. Mikula M, Dzwonek A, Karczmarski J, Rubel T, Dadlez M, Wyrwicz L, et al. Landscape of the hnRNP K protein-protein interactome. Proteomics. 2006;6:2395-406 pubmed
    ..These observations greatly expanded the view of the landscape of K protein-protein interaction and provide new opportunities to explore signal transduction and gene expression in several subcellular compartments. ..
  9. Nakatsuji H, Nishimura N, Yamamura R, Kanayama H, Sasaki T. Involvement of actinin-4 in the recruitment of JRAB/MICAL-L2 to cell-cell junctions and the formation of functional tight junctions. Mol Cell Biol. 2008;28:3324-35 pubmed publisher
    ..These results indicate that actinin-4 is involved in recruiting JRAB/MICAL-L2 to cell-cell junctions and forming functional TJs. ..

More Information


  1. Keicher C, Gambaryan S, Schulze E, Marcus K, Meyer H, Butt E. Phosphorylation of mouse LASP-1 on threonine 156 by cAMP- and cGMP-dependent protein kinase. Biochem Biophys Res Commun. 2004;324:308-16 pubmed
    ..Immunoblotting of LASP-1 in various mouse and human tissues detected a similar prominent expression in non-muscle tissue. Altogether, our data suggest so far no functional differences between human and mouse LASP-1. ..
  2. Geisert E, Yang L, Irwin M. Astrocyte growth, reactivity, and the target of the antiproliferative antibody, TAPA. J Neurosci. 1996;16:5478-87 pubmed
    ..The high levels of rTAPA at the site of CNS injury and the AMP1 antibody perturbation studies indicate that rTAPA may play a prominent role in the response of astrocytes to injury and in glial scar formation. ..
  3. Kigawa A, Wakui H, Maki N, Okuyama S, Masai R, Ohtani H, et al. Interaction of the spectrin-like repeats of alpha-actinin-4 with humanin peptide. Clin Exp Nephrol. 2004;8:331-8 pubmed
    ..Our results suggest that humanin is a novel binding partner of the actinin-4 R1-R4 domain in podocytes. Humanin and PAN are unlikely to compete for the same binding surface in actinin-4. ..
  4. Honda K, Yamada T, Endo R, Ino Y, Gotoh M, Tsuda H, et al. Actinin-4, a novel actin-bundling protein associated with cell motility and cancer invasion. J Cell Biol. 1998;140:1383-93 pubmed
    ..These findings suggest that cytoplasmic actinin-4 regulates the actin cytoskeleton and increases cellular motility and that its inactivation by transfer to the nucleus abolishes the metastatic potential of human cancers. ..
  5. Jayadev R, Kuk C, Low S, Murata Hori M. Calcium sensitivity of ?-actinin is required for equatorial actin assembly during cytokinesis. Cell Cycle. 2012;11:1929-37 pubmed publisher
    ..Our observations shed new light on the role and regulation of the accumulation of pre-existing actin filaments in equatorial actin assembly during cytokinesis. ..
  6. Ogneva I, Biryukov N, Leinsoo T, Larina I. Possible role of non-muscle alpha-actinins in muscle cell mechanosensitivity. PLoS ONE. 2014;9:e96395 pubmed publisher
    ..At the same time, the concentration of the abovementioned proteins decreased in the soleus muscle fibers. ..
  7. Geisert E, Murphy T, Irwin M, Larjava H. A novel cell adhesion molecule, G-CAM, found on cultured rat glia. Neurosci Lett. 1991;133:262-6 pubmed
    ..We have tentatively termed this molecule 'glial cell adhesion molecule' (G-CAM). ..
  8. Kim J, Lee Kwon W, Park J, Ryu S, Yun C, Donowitz M. Ca(2+)-dependent inhibition of Na+/H+ exchanger 3 (NHE3) requires an NHE3-E3KARP-alpha-actinin-4 complex for oligomerization and endocytosis. J Biol Chem. 2002;277:23714-24 pubmed
    ..From these results, we propose that elevated Ca(2+) inhibits NHE3 activity through oligomerization and endocytosis of NHE3, which occurs via formation of an NHE3-E3KARP-alpha-actinin-4 complex. ..
  9. Lehtonen S, Lehtonen E, Kudlicka K, Holthofer H, Farquhar M. Nephrin forms a complex with adherens junction proteins and CASK in podocytes and in Madin-Darby canine kidney cells expressing nephrin. Am J Pathol. 2004;165:923-36 pubmed
  10. Gokhin D, Lewis R, McKeown C, Nowak R, Kim N, Littlefield R, et al. Tropomodulin isoforms regulate thin filament pointed-end capping and skeletal muscle physiology. J Cell Biol. 2010;189:95-109 pubmed publisher
    ..Thus, Tmod3 and -4 compensate for the absence of Tmod1 structurally but not functionally. We conclude that Tmod1 is a novel regulator of skeletal muscle physiology. ..
  11. Honda K, Yamada T, Hayashida Y, Idogawa M, Sato S, Hasegawa F, et al. Actinin-4 increases cell motility and promotes lymph node metastasis of colorectal cancer. Gastroenterology. 2005;128:51-62 pubmed
    ..When injected into the mesocecum of severe combined immunodeficient mice, DLD1 Tet-off ACTN4 cells, but not the control cells, metastasized into regional mesenteric lymph nodes, resembling the behavior of ..
  12. Sakane A, Alamir Mahmoud Abdallah A, Nakano K, Honda K, Kitamura T, Imoto I, et al. Junctional Rab13-binding protein (JRAB) regulates cell spreading via filamins. Genes Cells. 2013;18:810-22 pubmed publisher
    ..However, actinin-1/-4 have no effect on the cell spreading regulated by JRAB?CC. These data suggest that JRAB contributes to the rearrangement of the actin cytoskeleton during cell spreading via filamins. ..
  13. Sun Y, Jaldin Fincati J, Liu Z, Bilan P, Klip A. A complex of Rab13 with MICAL-L2 and α-actinin-4 is essential for insulin-dependent GLUT4 exocytosis. Mol Biol Cell. 2016;27:75-89 pubmed publisher
    ..Insulin further increased binding of MICAL-L2 to α-actinin-4 (ACTN4), a protein involved in GLUT4 translocation...
  14. Menez J, Le Maux Chansac B, Dorothee G, Vergnon I, Jalil A, Carlier M, et al. Mutant alpha-actinin-4 promotes tumorigenicity and regulates cell motility of a human lung carcinoma. Oncogene. 2004;23:2630-9 pubmed
    The precise role of alpha-actinin-4 encoding gene (ACTN4) is not very well understood. It has been reported to elicit tumor suppressor activity and to regulate cellular motility...
  15. Kos C, Le T, Sinha S, Henderson J, Kim S, Sugimoto H, et al. Mice deficient in alpha-actinin-4 have severe glomerular disease. J Clin Invest. 2003;111:1683-90 pubmed
    Dominantly inherited mutations in ACTN4, which encodes alpha-actinin-4, cause a form of human focal and segmental glomerulosclerosis (FSGS). By homologous recombination in ES cells, we developed a mouse model deficient in Actn4...
  16. Ooshio T, Irie K, Morimoto K, Fukuhara A, Imai T, Takai Y. Involvement of LMO7 in the association of two cell-cell adhesion molecules, nectin and E-cadherin, through afadin and alpha-actinin in epithelial cells. J Biol Chem. 2004;279:31365-73 pubmed
    ..These results indicate that LMO7 is an afadin- and alpha-actinin-binding protein that connects the nectin-afadin and E-cadherin-catenin systems through alpha-actinin. ..
  17. Yang N, Schindeler A, McDonald M, Seto J, Houweling P, Lek M, et al. ?-Actinin-3 deficiency is associated with reduced bone mass in human and mouse. Bone. 2011;49:790-8 pubmed publisher
    ..Given the high frequency of R577X in the general population, the potential role of ACTN3 R577X as a factor influencing variations in BMD in elderly humans warrants further study. ..
  18. Michaud J, Chaisson K, Parks R, Kennedy C. FSGS-associated alpha-actinin-4 (K256E) impairs cytoskeletal dynamics in podocytes. Kidney Int. 2006;70:1054-61 pubmed
    Mutations in the ACTN4 gene, encoding the actin crosslinking protein alpha-actinin-4, are associated with a familial form of focal segmental glomerulosclerosis (FSGS)...
  19. Torrado M, Senatorov V, Trivedi R, Fariss R, Tomarev S. Pdlim2, a novel PDZ-LIM domain protein, interacts with alpha-actinins and filamin A. Invest Ophthalmol Vis Sci. 2004;45:3955-63 pubmed
    ..These results suggest that Pdlim2, like other ALP subfamily members, may act as an adapter that directs other proteins to the cytoskeleton. ..
  20. Talior Volodarsky I, Randhawa V, Zaid H, Klip A. Alpha-actinin-4 is selectively required for insulin-induced GLUT4 translocation. J Biol Chem. 2008;283:25115-23 pubmed publisher
    ..amino acid labeling and mass spectrometry, we observed insulin-dependent co-precipitation of actinin-4 (ACTN4) with GLUT4 (Foster, L. J., Rudich, A., Talior, I., Patel, N., Huang, X., Furtado, L. M., Bilan, P. J., Mann, M...
  21. Noda Y, Horikawa S, Katayama Y, Sasaki S. Identification of a multiprotein "motor" complex binding to water channel aquaporin-2. Biochem Biophys Res Commun. 2005;330:1041-7 pubmed
    ..Our findings show for the first time an AQP2-binding multiprotein "force generator" complex. This multiprotein complex may provide the machinery of driving AQP2 movement. ..
  22. Asanuma K, Kim K, Oh J, Giardino L, Chabanis S, Faul C, et al. Synaptopodin regulates the actin-bundling activity of alpha-actinin in an isoform-specific manner. J Clin Invest. 2005;115:1188-98 pubmed
    ..In concert, synaptopodin regulates the actin-bundling activity of alpha-actinin in highly dynamic cell compartments, such as podocyte FPs and the dendritic spine apparatus. ..
  23. Ehrlicher A, Krishnan R, Guo M, Bidan C, Weitz D, Pollak M. Alpha-actinin binding kinetics modulate cellular dynamics and force generation. Proc Natl Acad Sci U S A. 2015;112:6619-24 pubmed publisher
    ..Here we show that the binding affinity of the actin cross-linker α-actinin 4 (ACTN4) in cells modulates cytoplasmic mobility, cellular movement, and traction forces...
  24. Bijian K, Takano T, Papillon J, Le Berre L, Michaud J, Kennedy C, et al. Actin cytoskeleton regulates extracellular matrix-dependent survival signals in glomerular epithelial cells. Am J Physiol Renal Physiol. 2005;289:F1313-23 pubmed
    ..Appropriate remodeling of the actin cytoskeleton may be necessary for facilitating survival, as both disassembly and excessive crosslinking affect survival adversely. ..
  25. Cybulsky A, Takano T, Papillon J, Bijian K, Guillemette J, Kennedy C. Glomerular epithelial cell injury associated with mutant alpha-actinin-4. Am J Physiol Renal Physiol. 2009;297:F987-95 pubmed publisher
    ..In addition, alpha-actinin-4 K256E exacerbated apoptosis in the context of mild proteasome inhibition. Thus alpha-actinin-4 K256E triggers several metabolic abnormalities, which may lead to GEC injury and glomerulosclerosis. ..
  26. Ha T. High glucose and advanced glycosylated end-products affect the expression of alpha-actinin-4 in glomerular epithelial cells. Nephrology (Carlton). 2006;11:435-41 pubmed
  27. Kaplan J, Kim S, North K, Rennke H, Correia L, Tong H, et al. Mutations in ACTN4, encoding alpha-actinin-4, cause familial focal segmental glomerulosclerosis. Nat Genet. 2000;24:251-6 pubmed
    ..Here we present evidence implicating mutations in the gene encoding alpha-actinin-4 (ACTN4; ref...
  28. Sakane A, Honda K, Sasaki T. Rab13 regulates neurite outgrowth in PC12 cells through its effector protein, JRAB/MICAL-L2. Mol Cell Biol. 2010;30:1077-87 pubmed publisher
    ..These results suggest that Rab13 and JRAB/MICAL-L2 may act to transfer actinin-4 from the cell body to the tips of neurites, where actinin-4 is involved in the reorganization of the actin cytoskeleton which results in neurite outgrowth. ..
  29. Beqqali A, Monshouwer Kloots J, Monteiro R, Welling M, Bakkers J, Ehler E, et al. CHAP is a newly identified Z-disc protein essential for heart and skeletal muscle function. J Cell Sci. 2010;123:1141-50 pubmed publisher
    ..These findings suggest that CHAP is a critical component of the sarcomere with an important role in muscle development. ..
  30. Poliakov L, Malinskiĭ D, Kubakin V. [Complex evaluation of the health status indicators of military personnel]. Voen Med Zh. 1978;:15-20 pubmed
  31. Goto H, Wakui H, Komatsuda A, Ohtani H, Imai H, Sawada K, et al. Renal alpha-actinin-4: purification and puromycin aminonucleoside-binding property. Nephron Exp Nephrol. 2003;93:e27-35 pubmed
    ..Moreover, our findings indicate that the central rod domain of actinin-4 has a high affinity to PAN. In the PAN nephrosis animal model, actinin-4 might be a target protein from PAN nephrotoxicity. ..
  32. Irwin M, Geisert E. The upregulation of a glial cell surface antigen at the astrocytic scar in the rat. Neurosci Lett. 1993;154:57-60 pubmed
    ..The correlation between AMP1 antigen upregulation and reactive gliosis suggests that this molecule is critical to the process of CNS scar formation. ..