Gene Symbol: ACTN4
Description: actinin alpha 4
Alias: ACTININ-4, FSGS, FSGS1, alpha-actinin-4, focal segmental glomerulosclerosis 1, non-muscle alpha-actinin 4
Species: human
Products:     ACTN4

Top Publications

  1. Yamamoto S, Tsuda H, Honda K, Takano M, Tamai S, Imoto I, et al. ACTN4 gene amplification and actinin-4 protein overexpression drive tumour development and histological progression in a high-grade subset of ovarian clear-cell adenocarcinomas. Histopathology. 2012;60:1073-83 pubmed publisher
    Actinin-4, encoded by the ACTN4 gene located on chromosome 19q13.2, enhances cell motility by bundling the actin cytoskeleton...
  2. 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. ..
  3. 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
  4. Hayashida Y, Honda K, Idogawa M, Ino Y, Ono M, Tsuchida A, et al. E-cadherin regulates the association between beta-catenin and actinin-4. Cancer Res. 2005;65:8836-45 pubmed
    ..Shutting down the signals mediating this association may be worth considering as a therapeutic approach to cancer invasion and metastasis. ..
  5. 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...
  6. Yamamoto S, Tsuda H, Honda K, Kita T, Takano M, Tamai S, et al. Actinin-4 expression in ovarian cancer: a novel prognostic indicator independent of clinical stage and histological type. Mod Pathol. 2007;20:1278-85 pubmed
    ..Accumulation of actinin-4 in the cytoplasm may be related to a higher propensity for tumor invasiveness and metastasis, probably by enhancing cell motility, and could be a novel prognostic indicator for patients with ovarian carcinomas. ..
  7. Ihalmo P, Wessman M, Kaunisto M, Kilpikari R, Parkkonen M, Forsblom C, et al. Association analysis of podocyte slit diaphragm genes as candidates for diabetic nephropathy. Diabetologia. 2008;51:86-90 pubmed
    ..Here we report a genetic association analysis of four slit diaphragm genes, LRRC7, KIRREL, NPHS2 and ACTN4, in a Finnish diabetic nephropathy cohort...
  8. Watabe Y, Mori T, Yoshimoto S, Nomura T, Shibahara T, Yamada T, et al. Copy number increase of ACTN4 is a prognostic indicator in salivary gland carcinoma. Cancer Med. 2014;3:613-22 pubmed publisher
    Copy number increase (CNI) of ACTN4 has been associated with poor prognosis and metastatic phenotypes in various human carcinomas...
  9. Khotin M, Turoverova L, Aksenova V, Barlev N, Borutinskaite V, Vener A, et al. Proteomic analysis of ACTN4-interacting proteins reveals it's a putative involvement in mRNA metabolism. Biochem Biophys Res Commun. 2010;397:192-6 pubmed publisher
    Alpha-actinin 4 (ACTN4) is an actin-binding protein. In the cytoplasm, ACTN4 participates in structural organisation of the cytoskeleton via cross-linking of actin filaments...

More Information


  1. Khurana S, Chakraborty S, Cheng X, Su Y, Kao H. The actin-binding protein, actinin alpha 4 (ACTN4), is a nuclear receptor coactivator that promotes proliferation of MCF-7 breast cancer cells. J Biol Chem. 2011;286:1850-9 pubmed publisher
    ..We show here that ACTN4 harbors a functional LXXLL receptor interaction motif, interacts with nuclear receptors in vitro and in mammalian ..
  2. Shao H, Wu C, Wells A. Phosphorylation of alpha-actinin 4 upon epidermal growth factor exposure regulates its interaction with actin. J Biol Chem. 2010;285:2591-600 pubmed publisher
    ..that express human epidermal growth factor receptor (EGFR) and found that both alpha-actinin 1 (ACTN1) and alpha-actinin 4 (ACTN4) were phosphorylated on tyrosine residues after stimulation with EGF, although ACTN4 was phosphorylated ..
  3. Vallenius T, Luukko K, Mäkelä T. CLP-36 PDZ-LIM protein associates with nonmuscle alpha-actinin-1 and alpha-actinin-4. J Biol Chem. 2000;275:11100-5 pubmed
    ..More generally, results presented here demonstrate that the association of PDZ-LIM proteins with the cytoskeleton extends to the actin stress fibers of nonmuscle cells. ..
  4. Nikolopoulos S, Spengler B, Kisselbach K, Evans A, Biedler J, Ross R. The human non-muscle alpha-actinin protein encoded by the ACTN4 gene suppresses tumorigenicity of human neuroblastoma cells. Oncogene. 2000;19:380-6 pubmed
    ..a cDNA from human neuroblastoma cell variants which encodes the second non-muscle alpha-actinin isoform designated ACTN4 (actinin-4)...
  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. Yamada S, Yanamoto S, Yoshida H, Yoshitomi I, Kawasaki G, Mizuno A, et al. RNAi-mediated down-regulation of alpha-actinin-4 decreases invasion potential in oral squamous cell carcinoma. Int J Oral Maxillofac Surg. 2010;39:61-7 pubmed publisher
    ..The study indicated that alpha-actinin-4 could be a potential molecular target for gene therapy by RNAi targeting for OSCC. ..
  7. Noro R, Honda K, Tsuta K, Ishii G, Maeshima A, Miura N, et al. Distinct outcome of stage I lung adenocarcinoma with ACTN4 cell motility gene amplification. Ann Oncol. 2013;24:2594-600 pubmed publisher
    ..However, no method for distinguishing such tumors has yet been established. The copy number of the actinin-4 (ACTN4) gene was determined by fluorescence in situ hybridization on tissue microarrays comprising 543 surgically ..
  8. Yamamoto S, Tsuda H, Honda K, Onozato K, Takano M, Tamai S, et al. Actinin-4 gene amplification in ovarian cancer: a candidate oncogene associated with poor patient prognosis and tumor chemoresistance. Mod Pathol. 2009;22:499-507 pubmed publisher
    ..We hypothesized that the actinin-4 (ACTN4) gene might be a target of the 19q12-q13 amplicon and play an essential role of ovarian cancer progression...
  9. Babakov V, Petukhova O, Turoverova L, Kropacheva I, Tentler D, Bolshakova A, et al. RelA/NF-kappaB transcription factor associates with alpha-actinin-4. Exp Cell Res. 2008;314:1030-8 pubmed publisher
    ..We suggest that the alpha-actinin-4 is important for the NF-kappaB nuclear translocation and its functions inside the nucleus...
  10. Yoshii H, Ito K, Asano T, Horiguchi A, Hayakawa M, Asano T. Increased expression of ?-actinin-4 is associated with unfavorable pathological features and invasiveness of bladder cancer. Oncol Rep. 2013;30:1073-80 pubmed publisher
    In the present study, the association between clinicopathological parameters and ?-actinin-4 (ACTN4) expression in bladder cancer specimens was evaluated, and the functional role of ACTN4 in bladder cancer cells was investigated...
  11. 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. ..
  12. Chakraborty S, Reineke E, Lam M, Li X, Liu Y, Gao C, et al. Alpha-actinin 4 potentiates myocyte enhancer factor-2 transcription activity by antagonizing histone deacetylase 7. J Biol Chem. 2006;281:35070-80 pubmed
    ..The interaction domains are mapped to C terminus of alpha-actinin 4 and amino acids 72-172 of HDAC7...
  13. 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...
  14. Gonzalez A, Otey C, Edlund M, Jones J. Interactions of a hemidesmosome component and actinin family members. J Cell Sci. 2001;114:4197-206 pubmed
    ..We discuss a role for BP180 in crosstalk between cell-matrix and cell-cell junctions. ..
  15. Patrie K, Drescher A, Welihinda A, Mundel P, Margolis B. Interaction of two actin-binding proteins, synaptopodin and alpha-actinin-4, with the tight junction protein MAGI-1. J Biol Chem. 2002;277:30183-90 pubmed
    ..The interaction and colocalization of MAGI-1 with two actin-bundling proteins suggest that MAGI-1 may play a role in actin cytoskeleton dynamics within polarized epithelial cells. ..
  16. Sen S, Dong M, Kumar S. Isoform-specific contributions of alpha-actinin to glioma cell mechanobiology. PLoS ONE. 2009;4:e8427 pubmed publisher
  17. Otey C, Pavalko F, Burridge K. An interaction between alpha-actinin and the beta 1 integrin subunit in vitro. J Cell Biol. 1990;111:721-9 pubmed
    ..These results lead us to suggest that this integrin-alpha-actinin linkage may contribute to the attachment of actin filaments to the membrane in certain locations. ..
  18. Khurana S, Chakraborty S, Zhao X, Liu Y, Guan D, Lam M, et al. Identification of a novel LXXLL motif in ?-actinin 4-spliced isoform that is critical for its interaction with estrogen receptor ? and co-activators. J Biol Chem. 2012;287:35418-29 pubmed publisher
    ..Recently, it has also become clear that ACTN4 can function in the nucleus...
  19. 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...
  20. Kikuchi S, Honda K, Tsuda H, Hiraoka N, Imoto I, Kosuge T, et al. Expression and gene amplification of actinin-4 in invasive ductal carcinoma of the pancreas. Clin Cancer Res. 2008;14:5348-56 pubmed publisher
    ..The copy number of the actinin-4 (ACTN4) gene was calculated by fluorescence in situ hybridization...
  21. Barbolina M, Adley B, Kelly D, Fought A, Scholtens D, Shea L, et al. Motility-related actinin alpha-4 is associated with advanced and metastatic ovarian carcinoma. Lab Invest. 2008;88:602-14 pubmed publisher
    ..The role of actinin alpha-4 (ACTN4), a cytoskeleton-associated protein implicated in the regulation of cell motility, was examined in detail...
  22. Welsch T, Keleg S, Bergmann F, Bauer S, Hinz U, Schmidt J. Actinin-4 expression in primary and metastasized pancreatic ductal adenocarcinoma. Pancreas. 2009;38:968-76 pubmed publisher
    ..Actinin-4 expression levels significantly correlate with worse survival after PDAC resection. Although actinin-4 has been reported to promote lymph node metastases, there was no enhanced expression in PDAC metastases. ..
  23. Quick Q, Skalli O. Alpha-actinin 1 and alpha-actinin 4: contrasting roles in the survival, motility, and RhoA signaling of astrocytoma cells. Exp Cell Res. 2010;316:1137-47 pubmed publisher
    ..of astrocytomas, as alpha-actinin 1 was higher in astrocytomas compared to normal brains whereas alpha-actinin 4 was elevated in high-grade astrocytomas compared to normal brains and low grade astrocytomas...
  24. Lichtnekert J, Kaverina N, Eng D, Gross K, Kutz J, Pippin J, et al. Renin-Angiotensin-Aldosterone System Inhibition Increases Podocyte Derivation from Cells of Renin Lineage. J Am Soc Nephrol. 2016;27:3611-3627 pubmed
    ..We then induced experimental FSGS, typified by abrupt podocyte depletion, with a cytopathic antipodocyte antibody...
  25. Sun H, Al Romaih K, Macrae C, Pollak M. Human Kidney Disease-causing INF2 Mutations Perturb Rho/Dia Signaling in the Glomerulus. EBioMedicine. 2014;1:107-15 pubmed publisher
    ..formin family protein that regulates actin cytoskeleton dynamics, cause focal segmental glomerulosclerosis (FSGS) and Charcot-Marie-Tooth Disease (CMT) in humans...
  26. Webster P, Webster L, Cook H, Horsfield C, Seed P, Vaz R, et al. A Multicenter Cohort Study of Histologic Findings and Long-Term Outcomes of Kidney Disease in Women Who Have Been Pregnant. Clin J Am Soc Nephrol. 2017;12:408-416 pubmed publisher
    ..b>FSGS was more common in pregnancy-related biopsies (32.4%) than controls (9.7%) (P<0...
  27. Schaefer A, Te Riet J, Ritz K, Hoogenboezem M, Anthony E, Mul F, et al. Actin-binding proteins differentially regulate endothelial cell stiffness, ICAM-1 function and neutrophil transmigration. J Cell Sci. 2014;127:4470-82 pubmed publisher
    ..These results identify endothelial cell stiffness as an important regulator of endothelial surface heterogeneity and of ICAM-1 function, which in turn controls the adhesion and transmigration of neutrophils. ..
  28. Miao L, Wei D, Zhang Y, Liu J, Lu S, Zhang A, et al. Effects of stromal interaction molecule 1 or Orai1 overexpression on the associated proteins and permeability of podocytes. Nephrology (Carlton). 2016;21:959-967 pubmed publisher
    ..Our findings suggested that STIM1/Orai1 overexpression could affect the cell permeability and the expression of partial podocyte-associated proteins, which may ultimately result in podocyte injury. ..
  29. Wang N, Wang Q, Tang H, Zhang F, Zheng Y, Wang S, et al. Direct inhibition of ACTN4 by ellagic acid limits breast cancer metastasis via regulation of ?-catenin stabilization in cancer stem cells. J Exp Clin Cancer Res. 2017;36:172 pubmed publisher
    ..The current study sought to determine the role and regulation of ACTN4 expression in human breast cancer metastasis and EA-based therapy...
  30. Kalavrizioti D, Gerolymos M, Rodi M, Kalliakmani P, Provatopoulou S, Eleftheriadis T, et al. T helper (Th)-cytokines in the urine of patients with primary glomerulonephritis treated with immunosuppressive drugs: Can they predict outcome?. Cytokine. 2015;76:260-269 pubmed publisher
    ..MN, n=36), IgA nephropathy (IgAN, n=31) and minimal changes disease or focal segmental glomerulosclerosis (MCD/FSGS, n=30)...
  31. Srinivas V, Murata Hori M. Proper positioning of the cleavage furrow requires ?-actinin to regulate the specification of different populations of microtubules. J Cell Sci. 2012;125:4713-9 pubmed publisher
    ..Our findings unveil an unexpected yet crucial role for an actin crosslinking protein in the regulation of the localization of the microtubule-associated cytokinetic regulator. ..
  32. Husain S. Collapsing glomerulopathy, the Saudi Arabian scenario. A study of 31 cases and a review of literature. Saudi Med J. 2017;38:509-516 pubmed publisher
    ..The number of glomeruli with collapsing lesions per biopsy ranged from 1 to 9. Other types of FSGS lesions (not otherwise specified and perihilar) were also noted. There was extensive podocyte effacement...
  33. Zhang Y, Gu Q, Huang J, Qu Z, Wang X, Meng L, et al. Clinical Significance of IgM and C3 Glomerular Deposition in Primary Focal Segmental Glomerulosclerosis. Clin J Am Soc Nephrol. 2016;11:1582-9 pubmed publisher
    Glomerular IgM deposition is commonly shown in primary FSGS and sometimes accompanied by C3 deposition. Clinical presentation and treatment outcomes of these patients are not investigated in detail...
  34. Won K, Im J, Kim B, Ban H, Jung Y, Jung K, et al. Stability of the cancer target DDIAS is regulated by the CHIP/HSP70 pathway in lung cancer cells. Cell Death Dis. 2017;8:e2554 pubmed publisher
  35. Kumar A, Srilakshmi R, Karthickeyan S, Balakrishnan K, Padmaraj R, Senguttuvan P. Wilms' tumour 1 gene mutations in south Indian children with steroid-resistant nephrotic syndrome. Indian J Med Res. 2016;144:276-280 pubmed publisher
    ..Renal histology analysis showed two cases with focal segmental glomerulosclerosis (FSGS) and they had external female genitalia but 46,XY karyotype. Both of them had streak gonads...
  36. Sun L, Zheng J, Wang Q, Song R, Liu H, Meng R, et al. NHERF1 regulates actin cytoskeleton organization through modulation of α-actinin-4 stability. FASEB J. 2016;30:578-89 pubmed publisher
    ..Our study identified α-actinin-4 as a novel NHERF1 interaction partner and provided new insights into the regulatory mechanism of the actin cytoskeleton by NHERF1. ..
  37. Chen J, Chang L, Wu C, Tseng T, Lin J, Lin Y, et al. Significance of the urokinase-type plasminogen activator and its receptor in the progression of focal segmental glomerulosclerosis in clinical and mouse models. J Biomed Sci. 2016;23:24 pubmed publisher
    suPAR biomarker generally considered a pathogenic factor in FSGS. However, studies have been published that dispute this conclusion...
  38. Yee A, Papillon J, Guillemette J, Kaufman D, Kennedy C, Cybulsky A. Proteostasis as a Therapeutic Target in Glomerular Injury Associated with Mutant Alpha-Actinin-4. Am J Physiol Renal Physiol. 2018;: pubmed publisher
    Mutations in alpha-actinin-4 (actinin-4) result in hereditary focal segmental glomerulosclerosis (FSGS) in humans. Actinin-4 mutants induce podocyte injury due to dysregulation of the cytoskeleton and proteotoxicity...
  39. Yamaguchi H, Ito Y, Miura N, Nagamura Y, Nakabo A, Fukami K, et al. Actinin-1 and actinin-4 play essential but distinct roles in invadopodia formation by carcinoma cells. Eur J Cell Biol. 2017;96:685-694 pubmed publisher
    ..These results demonstrate that both actinin-1 and actinin-4 participate in the assembly of F-actin at invadopodia. Additionally, actinin-4 may have a selective advantage in accelerating invadopodia-mediated invasion of carcinoma cells. ..
  40. Ma F, Sun T, Wu M, Wang W, Xu Z. Identification of key genes for diabetic kidney disease using biological informatics methods. Mol Med Rep. 2017;16:7931-7938 pubmed publisher
    ..Vascular endothelial growth factor A (VEGFA), ??actinin?4 (ACTN4), proto?oncogene, Src family tyrosine kinase (FYN), collagen, type 1, ?2 (COL1A2) and insulin?like growth factor 1 ..
  41. Liao Q, Li R, Zhou R, Pan Z, Xu L, Ding Y, et al. LIM kinase 1 interacts with myosin-9 and alpha-actinin-4 and promotes colorectal cancer progression. Br J Cancer. 2017;117:563-571 pubmed publisher
    ..Furthermore, we identified two tumour metastasis-associated proteins, MYH9 and ACTN4, as direct targets of LIMK1, which were required for a LIMK1-mediated aggressive phenotype...
  42. Kolonko A, Piecha G, Wiecek A. Successful Preemptive Kidney Transplantation With Rituximab Induction in a Patient With Focal Segmental Glomerulosclerosis and Massive Nephrotic Syndrome: A Case Report. Transplant Proc. 2016;48:3092-3094 pubmed publisher
    Primary focal segmental glomerulosclerosis (FSGS) recurs in 30% of patients receiving their first kidney transplant and often leads to graft loss...
  43. Ren H, Lin L, Shen P, Li X, Xie J, Pan X, et al. Rituximab treatment in adults with refractory minimal change disease or focal segmental glomerulosclerosis. Oncotarget. 2017;8:93438-93443 pubmed publisher
    Rituximab (RTX) may benefit patients with glomerular disease who suffer from focal segmental glomerular sclerosis (FSGS) or minimal change disease (MCD)...
  44. Magdolen U, Schroeck F, Creutzburg S, Schmitt M, Magdolen V. Non-muscle alpha-actinin-4 interacts with plasminogen activator inhibitor type-1 (PAI-1). Biol Chem. 2004;385:801-8 pubmed
    ..We suggest that PAI-1, via interaction with both Act-4 and uPA, may function as a modulator of this mononuclear phagocyte response, not only in inflammation but also in tumor invasion and metastasis. ..
  45. Kaverina N, Eng D, Largent A, Daehn I, Chang A, Gross K, et al. WT1 Is Necessary for the Proliferation and Migration of Cells of Renin Lineage Following Kidney Podocyte Depletion. Stem Cell Reports. 2017;9:1152-1166 pubmed publisher
    ..following podocyte depletion in three experimental models, and in patients with focal segmental glomerulosclerosis (FSGS) and membranous nephropathy, WT1 increased significantly in cells of renin lineage (CoRL)...
  46. Kemper M, Valentin L, van Husen M. Difficult-to-treat idiopathic nephrotic syndrome: established drugs, open questions and future options. Pediatr Nephrol. 2018;33:1641-1649 pubmed publisher
    ..disease (MCD) histology, whereas in steroid-resistant nephrotic syndrome (SRNS) focal segmental glomerulosclerosis (FSGS) is the most prevalent lesion...
  47. Alcubilla Prats P, Sole M, Botey A, Grau J, Garrabou G, Poch E. Kidney involvement in MELAS syndrome: Description of 2 cases. Med Clin (Barc). 2017;148:357-361 pubmed publisher
    ..a A3243G mutation also suffer from renal dysfunction, usually in form of focal segmental glomerulosclerosis (FSGS). In this study we examine kidney involvement in 2 unrelated patients with a A3243G mutation by genetic testing...
  48. Fencl F, Vondrák K, Rosík T, Zieg J, Chadimová M, Háček J, et al. Recurrence of nephrotic proteinuria in children with focal segmental glomerulosclerosis: early treatment with plasmapheresis and immunoadsorption should be associated with better prognosis. Minerva Pediatr. 2016;68:348-54 pubmed
    Primary focal segmental glomerulosclerosis (FSGS) is a glomerular disease, characterized by progressive renal function deterioration, nephrotic proteinuria, and risk of chronic renal failure...
  49. Jeon Y, Lee W, Choi Y, Kang S, Kim M, Lim S, et al. Crystalloid podocytopathy with focal segmental glomerulosclerosis in PCM: a case report. Diagn Pathol. 2015;10:213 pubmed publisher
    ..Crystalloid podocytopathy is a likely cause of renal damage such as FSGS in PCM, although it is an uncommon mechanism for myeloma kidney.
  50. Dai S, Wang Z, Pan X, Wang W, Chen X, Ren H, et al. Functional analysis of promoter mutations in the ACTN4 and SYNPO genes in focal segmental glomerulosclerosis. Nephrol Dial Transplant. 2010;25:824-35 pubmed publisher
    To investigate the promoter mutations of ACTN4 and SYNPO genes in patients with idiopathic focal segmental glomerulosclerosis (FSGS), and to provide functional analysis of these mutations in the role of FSGS occurrence...
  51. Kaverina N, Kadoya H, Eng D, Rusiniak M, Sequeira Lopez M, Gomez R, et al. Tracking the stochastic fate of cells of the renin lineage after podocyte depletion using multicolor reporters and intravital imaging. PLoS ONE. 2017;12:e0173891 pubmed publisher
    Podocyte depletion plays a major role in focal segmental glomerular sclerosis (FSGS)...
  52. Mundel P. Podocytes and the quest for precision medicines for kidney diseases. Pflugers Arch. 2017;469:1029-1037 pubmed publisher
    ..of the podocyte in many kidney diseases characterized by proteinuria, including focal segmental glomerulosclerosis (FSGS) and diabetic nephropathy, had not yet been recognized...
  53. Ding Z, Liang J, Lu Y, Yu Q, Songyang Z, Lin S, et al. A retrovirus-based protein complementation assay screen reveals functional AKT1-binding partners. Proc Natl Acad Sci U S A. 2006;103:15014-9 pubmed
    ..We confirm that alpha-actinin 4 (ACTN4) interacts physically and functionally with AKT1...
  54. Poch M, Al Kassim L, Smolinski S, Hines R. Two distinct classes of CCAAT box elements that bind nuclear factor-Y/alpha-actinin-4: potential role in human CYP1A1 regulation. Toxicol Appl Pharmacol. 2004;199:239-50 pubmed
    ..An approximate 106-kDa protein was purified and shown to be alpha-actinin-4 (ACTN4), one of two ubiquitously expressed non-muscle actinins...
  55. Büscher A, Celebi N, Hoyer P, Klein H, Weber S, Hoefele J. Mutations in INF2 may be associated with renal histology other than focal segmental glomerulosclerosis. Pediatr Nephrol. 2018;33:433-437 pubmed publisher
    ..We performed mutational analysis of ACTN4, CD2AP, COQ6, INF2, LAMB2, NPHS1, NPHS2, PLCE1, TRPC6, and WT1 in the index patient by next-generation sequencing...
  56. Zhong Z, Mao S, Lin H, Lin J, Lin J. Comparative proteomics of cancer stem cells in osteosarcoma using ultra-high-performance liquid chromatography and Orbitrap Fusion mass spectrometer. Talanta. 2018;178:362-368 pubmed publisher
    ..Selected differential ?-actinin 4 (ACTN4) proteins were validated by Western blot assay...
  57. Ou L, Przybilla M, Whitley C. Proteomic analysis of mucopolysaccharidosis I mouse brain with two-dimensional polyacrylamide gel electrophoresis. Mol Genet Metab. 2017;120:101-110 pubmed publisher
    ..Cytoskeletal proteins including ACTA1, ACTN4, TUBB4B and DNM1 were significantly downregulated...
  58. Bostrom M, Perlegas P, Lu L, Hicks P, Hawkins G, Ng M, et al. Relevance of the ACTN4 gene in African-Americans with non-diabetic end-stage renal disease. Am J Nephrol. 2012;36:252-60 pubmed publisher
    ..Rare mutations in ACTN4 (?-actinin-4), an actin-binding protein expressed in podocytes, cause familial focal segmental glomerulosclerosis...
  59. Bois P, Borgon R, Vonrhein C, Izard T. Structural dynamics of alpha-actinin-vinculin interactions. Mol Cell Biol. 2005;25:6112-22 pubmed
    ..The data suggest a model where vinculin's Vh1 domain acts as a molecular switch that undergoes distinct structural changes provoked by talin and alpha-actinin binding in focal adhesions versus adherens junctions, respectively. ..
  60. Raij L, Tian R, Wong J, He J, Campbell K. Podocyte injury: the role of proteinuria, urinary plasminogen, and oxidative stress. Am J Physiol Renal Physiol. 2016;311:F1308-F1317 pubmed publisher proteinuric glomerular diseases that result in podocyte loss, progressive focal segmental glomerular sclerosis (FSGS), and renal failure...
  61. Henry W, Dubois J, Quick Q. The microtubule inhibiting agent epothilone B antagonizes glioma cell motility associated with reorganization of the actin-binding protein ?-actinin 4. Oncol Rep. 2011;25:887-93 pubmed publisher
    ..techniques we demonstrated that epothilone B abrogated glioblastoma cell motility as a consequence of ?-actinin 4 redistristrubiton and the breakdown of cellular structures (leading edge, stress fibers) it is associated with ..
  62. Fukumoto M, Kurisu S, Yamada T, Takenawa T. α-Actinin-4 enhances colorectal cancer cell invasion by suppressing focal adhesion maturation. PLoS ONE. 2015;10:e0120616 pubmed publisher
    ..Among the four isoforms of mammalian ACTNs, ACTN1 and ACTN4 are ubiquitously expressed. Recently, ACTN4 was reported to enhance cancer cell motility, invasion, and metastasis...
  63. Lu Z, Zhang Y, Yan X, Chen Y, Tao X, Wang J, et al. Estrogen stimulates the invasion of ovarian cancer cells via activation of the PI3K/AKT pathway and regulation of its downstream targets E‑cadherin and α‑actinin‑4. Mol Med Rep. 2014;10:2433-40 pubmed publisher
    ..Inhibiting the PI3K/AKT pathway may be a useful treatment for ovarian carcinoma. ..
  64. Agarwal N, Adhikari A, Iyer S, Hekmatdoost K, Welch D, Iwakuma T. MTBP suppresses cell migration and filopodia formation by inhibiting ACTN4. Oncogene. 2013;32:462-70 pubmed publisher
    ..Co-immunoprecipitation and mass spectrometric analysis identified alpha-actinin-4 (ACTN4) as an MTBP-interacting protein. Endogenous MTBP interacted with and partially colocalized with ACTN4...
  65. Limou S, Vince N, Parsa A. Lessons from CKD-Related Genetic Association Studies-Moving Forward. Clin J Am Soc Nephrol. 2018;13:140-152 pubmed publisher
    ..g., IgA nephropathy, membranous nephropathy, FSGS)...
  66. 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
    ..and confocal microscopy, we demonstrated in normoxia, but not in hypoxia, an interaction between iNOS and alpha-actinin 4, an adapter protein that anchors enzymes to the actin cytoskeleton...
  67. Veettil M, Kumar B, Ansari M, Dutta D, Iqbal J, Gjyshi O, et al. ESCRT-0 Component Hrs Promotes Macropinocytosis of Kaposi's Sarcoma-Associated Herpesvirus in Human Dermal Microvascular Endothelial Cells. J Virol. 2016;90:3860-3872 pubmed publisher
    ..These studies demonstrate that the localization of Hrs from the cytosol to the plasma membrane is important for coupling membrane dynamics to the cytosolic signaling events during macropinocytosis of KSHV. ..
  68. Fróes B, de Almeida Araújo S, Bambirra E, Oliveira E, Simoes e Silva A, Pinheiro S. Is CD44 in glomerular parietal epithelial cells a pathological marker of renal function deterioration in primary focal segmental glomerulosclerosis?. Pediatr Nephrol. 2017;32:2165-2169 pubmed publisher
    The search for risk factors for chronic kidney disease in children with focal segmental glomerulosclerosis (FSGS) is important in defining prognosis and individualized treatment...
  69. Weins A, Kenlan P, Herbert S, Le T, Villegas I, Kaplan B, et al. Mutational and Biological Analysis of alpha-actinin-4 in focal segmental glomerulosclerosis. J Am Soc Nephrol. 2005;16:3694-701 pubmed
    Mutations in the alpha-actinin-4 gene (ACTN4) cause an autosomal dominant form of focal segmental glomerulosclerosis (FSGS)...
  70. Isobe S, Ohashi N, Katahashi N, Ishigaki S, Tsuji N, Tsuji T, et al. Focal segmental glomerulosclerosis associated with cutaneous and systemic plasmacytosis. CEN Case Rep. 2017;6:206-209 pubmed publisher
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