Gene Symbol: Actn4
Description: actinin alpha 4
Alias: C77391, alpha-actinin-4, F-actin cross-linking protein, non-muscle alpha-actinin 4
Species: mouse
Products:     Actn4

Top Publications

  1. 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...
  2. Dandapani S, Sugimoto H, Matthews B, Kolb R, Sinha S, Gerszten R, et al. Alpha-actinin-4 is required for normal podocyte adhesion. J Biol Chem. 2007;282:467-77 pubmed
    Mutations in the alpha-actinin-4 gene ACTN4 cause an autosomal dominant human kidney disease...
  3. 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. ..
  4. Michaud J, Lemieux L, Dubé M, Vanderhyden B, Robertson S, Kennedy C. Focal and segmental glomerulosclerosis in mice with podocyte-specific expression of mutant alpha-actinin-4. J Am Soc Nephrol. 2003;14:1200-11 pubmed
    Mutations in the gene encoding alpha-actinin-4 (ACTN4), an actin crosslinking protein, are associated with a form of autosomal dominant focal segmental glomerulosclerosis (FSGS)...
  5. Kumeta M, Yoshimura S, Harata M, Takeyasu K. Molecular mechanisms underlying nucleocytoplasmic shuttling of actinin-4. J Cell Sci. 2010;123:1020-30 pubmed publisher
  6. 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 ..
  7. Dear T, Meier N, Hunn M, Boehm T. Gene structure, chromosomal localization, and expression pattern of Capn12, a new member of the calpain large subunit gene family. Genomics. 2000;68:152-60 pubmed
    ..The last exon of the mouse Actn4 gene overlaps the 3' end of Capn12 but in the opposite orientation...
  8. Feng D, Notbohm J, Benjamin A, He S, Wang M, Ang L, et al. Disease-causing mutation in ?-actinin-4 promotes podocyte detachment through maladaptation to periodic stretch. Proc Natl Acad Sci U S A. 2018;115:1517-1522 pubmed publisher
    Actinin-4 (ACTN4) bundles and cross-links actin filaments to confer mechanical resilience to the reconstituted actin network...
  9. Read N, Gutsol A, Holterman C, Carter A, Coulombe J, Gray D, et al. Ubiquitin C-terminal hydrolase L1 deletion ameliorates glomerular injury in mice with ACTN4-associated focal segmental glomerulosclerosis. Biochim Biophys Acta. 2014;1842:1028-40 pubmed publisher
    ..In the present study, we tested whether UCHL1 is expressed in podocytes of a mouse model of ACTN4-associated FSGS. Podocyte UCHL1 protein was detected in glomeruli of K256E-ACTN4(pod+)/UCHL1+/+ mice...

More Information


  1. Zou X, Cheng H, Zhang Y, Fang C, Xia Y. The antigen-binding fragment of anti-double-stranded DNA IgG enhances F-actin formation in mesangial cells by binding to alpha-actinin-4. Exp Biol Med (Maywood). 2012;237:1023-31 pubmed
  2. Liu H, Gao X, Xu H, Feng C, Kuang X, Li Z, et al. ?-Actinin-4 is involved in the process by which dexamethasone protects actin cytoskeleton stabilization from adriamycin-induced podocyte injury. Nephrology (Carlton). 2012;17:669-75 pubmed publisher
    ..This study showed that dexamethasone had direct effects on podocytes: ?-actinin-4 may be one of the potential target molecules. ..
  3. 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. ..
  4. 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. ..
  5. 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. ..
  6. Cui X, Li X, Shen X, Bae Y, Kang J, Kim N. Transcription profile in mouse four-cell, morula, and blastocyst: Genes implicated in compaction and blastocoel formation. Mol Reprod Dev. 2007;74:133-43 pubmed
    ..The identification of the genes being expressed in here will provide insight into the complex gene regulatory networks effecting compaction and blastocoel formation...
  7. Ryu J, Kim H, Lee S, Chang E, Kim H, Kim H. Proteomic identification of the TRAF6 regulation of vacuolar ATPase for osteoclast function. Proteomics. 2005;5:4152-60 pubmed
    ..Our study identified V-ATPase as a TRAF6-binding protein using a proteomics strategy and proved a direct link between these two important molecules for osteoclast function. ..
  8. 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. ..
  9. 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...
  10. Nygren J, Liuba K, Breitbach M, Stott S, Thorén L, Roell W, et al. Myeloid and lymphoid contribution to non-haematopoietic lineages through irradiation-induced heterotypic cell fusion. Nat Cell Biol. 2008;10:584-92 pubmed publisher
    ..Our findings demonstrate that blood cells of the lymphoid and myeloid lineages contribute to various non-haematopoietic tissues by forming rare fusion hybrids, but almost exclusively in response to injuries or inflammation. ..
  11. Grgic I, Hofmeister A, Genovese G, Bernhardy A, Sun H, Maarouf O, et al. Discovery of new glomerular disease-relevant genes by translational profiling of podocytes in vivo. Kidney Int. 2014;86:1116-29 pubmed publisher
    ..This TRAP protocol robustly enriched known podocyte-specific mRNAs. We crossed Col1α1-eGFP-L10a mice with the Actn4(-/-) and Actn4(+/K256E) models of FSGS and analyzed podocyte transcriptional profiles at 2, 6, and 44 weeks of age...
  12. 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)...
  13. 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. ..
  14. Huttelmaier S, Illenberger S, Grosheva I, Rudiger M, Singer R, Jockusch B. Raver1, a dual compartment protein, is a ligand for PTB/hnRNPI and microfilament attachment proteins. J Cell Biol. 2001;155:775-86 pubmed
    ..During muscle differentiation, raver1 migrates from the nucleus to the costamere. We propose that raver1 may coordinate RNA processing and targeting as required for microfilament anchoring in specific adhesion sites. ..
  15. Roca Cusachs P, Del Rio A, Puklin Faucher E, Gauthier N, Biais N, Sheetz M. Integrin-dependent force transmission to the extracellular matrix by ?-actinin triggers adhesion maturation. Proc Natl Acad Sci U S A. 2013;110:E1361-70 pubmed publisher
    ..Such a multistep process enables cells to adjust forces on matrices, unveiling a role of ?-actinin that is different from its well-studied function as an actin cross-linker. ..
  16. Henderson J, Al Waheeb S, Weins A, Dandapani S, Pollak M. Mice with altered alpha-actinin-4 expression have distinct morphologic patterns of glomerular disease. Kidney Int. 2008;73:741-50 pubmed publisher
    Mutations in ACTN4, encoding the actin-binding protein alpha-actinin-4, cause a form of familial focal segmental glomerulosclerosis...
  17. An H, Kim J, Yoo S, Ko J. Small leucine zipper protein (sLZIP) negatively regulates skeletal muscle differentiation via interaction with ?-actinin-4. J Biol Chem. 2014;289:4969-79 pubmed publisher
    ..However, the role of sLZIP in myogenesis is unknown. We identified ?-actinin-4 (ACTN4) as a sLZIP-binding protein...
  18. Foley K, Young P. An analysis of splicing, actin-binding properties, heterodimerization and molecular interactions of the non-muscle ?-actinins. Biochem J. 2013;452:477-88 pubmed publisher
    ..This significantly alters our view of non-muscle actinin function. ..
  19. Weins A, SCHLONDORFF J, Nakamura F, Denker B, Hartwig J, Stossel T, et al. Disease-associated mutant alpha-actinin-4 reveals a mechanism for regulating its F-actin-binding affinity. Proc Natl Acad Sci U S A. 2007;104:16080-5 pubmed
  20. 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. ..
  21. 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. ..
  22. Shao H, Wang J, Pollak M, Wells A. ?-actinin-4 is essential for maintaining the spreading, motility and contractility of fibroblasts. PLoS ONE. 2010;5:e13921 pubmed publisher
    ..Most non-muscle cells such as fibroblasts express two isoforms, ?-actinin-1 (ACTN1) and ?-actinin-4 (ACTN4)...
  23. Chen V, Li X, Perreault H, Nagy J. Interaction of zonula occludens-1 (ZO-1) with alpha-actinin-4: application of functional proteomics for identification of PDZ domain-associated proteins. J Proteome Res. 2006;5:2123-34 pubmed
  24. Schiffer M, Teng B, Gu C, Shchedrina V, Kasaikina M, Pham V, et al. Pharmacological targeting of actin-dependent dynamin oligomerization ameliorates chronic kidney disease in diverse animal models. Nat Med. 2015;21:601-9 pubmed publisher
  25. Sadl V, Jin F, Yu J, Cui S, Holmyard D, Quaggin S, et al. The mouse Kreisler (Krml1/MafB) segmentation gene is required for differentiation of glomerular visceral epithelial cells. Dev Biol. 2002;249:16-29 pubmed
    ..However, these observations alone are unlikely to account for the aberrant podocyte foot process formation. Thus, Kreisler must regulate other unknown genes required for podocyte function and with possible roles in kidney disease. ..
  26. 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. ..
  27. Yao J, Le T, Kos C, Henderson J, Allen P, Denker B, et al. Alpha-actinin-4-mediated FSGS: an inherited kidney disease caused by an aggregated and rapidly degraded cytoskeletal protein. PLoS Biol. 2004;2:e167 pubmed
    ..Point mutations in the alpha-actinin-4 gene ACTN4 cause an autosomal dominant form of human FSGS...
  28. Shao H, Travers T, Camacho C, Wells A. The carboxyl tail of alpha-actinin-4 regulates its susceptibility to m-calpain and thus functions in cell migration and spreading. Int J Biochem Cell Biol. 2013;45:1051-63 pubmed publisher alpha-actinin-4, as well as binding of alpha-actinin-4 to actin filaments all inhibit m-calpain cleavage of ACTN4 between tyrosine 13 and glycine 14...
  29. Burgueno J, Blake D, Benson M, Tinsley C, Esapa C, Canela E, et al. The adenosine A2A receptor interacts with the actin-binding protein alpha-actinin. J Biol Chem. 2003;278:37545-52 pubmed
    ..These findings suggest an alpha-actinin-dependent association between the actin cytoskeleton and A2AR trafficking. ..
  30. Collin G, Marshall J, King B, Milan G, Maffei P, Jagger D, et al. The Alström syndrome protein, ALMS1, interacts with ?-actinin and components of the endosome recycling pathway. PLoS ONE. 2012;7:e37925 pubmed publisher
    ..Our results suggest a role for ALMS1 variants in the recycling endosome pathway and give us new insights into the pathogenesis of a subset of clinical phenotypes associated with ALMS. ..
  31. 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. ..
  32. 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...
  33. 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. ..
  34. Zhao Z, Deocharan B, Scherer P, Ozelius L, Putterman C. Differential binding of cross-reactive anti-DNA antibodies to mesangial cells: the role of alpha-actinin. J Immunol. 2006;176:7704-14 pubmed
    ..Modulation of Ag expression may be a promising approach to down-regulate immune complex formation in the target organ in individuals with circulating pathogenic Abs. ..
  35. Yu H, Li Z, Ghosh D, Lim T, He Y, Lin Q. ?-Actinin4 nuclear translocation mediates gonadotropin-releasing hormone stimulation of follicle-stimulating hormone ?-subunit gene transcription in L?T2 cells. FEBS Lett. 2012;586:1466-71 pubmed publisher
    ..Our iTRAQ quantitative proteomics result showed that the abundance of ?-actinin4 (ACTN4) increased in the nuclei of L?T2 cells upon GnRH induction...