Alpha-actinin: A multidisciplinary protein with important role in B-cell driven autoimmunity
Alpha-actinin (α-actinin) is a ubiquitous cytoskeletal protein, which belongs to the superfamily of filamentous actin (F-actin) crosslinking proteins. It is present in multiple subcellular regions of both muscle and non-muscle cells, including cell-cell and cell-matrix contact sites, cellular protrusions and stress fiber dense regions and thus, it seems to bear multiple important roles in the cell by linking the cytoskeleton to many different transmembrane proteins in a variety of junctions. Four isoforms of human α-actinin have already been identified namely, the "muscles" α-actinin-2 and α-actinin-3 and the "non-muscles" α-actinin-1 and α-actinin-4. The precise functions of α-actinin isoforms as well as the precise role and significance of their binding to F-actin particularly in-vivo, have been elusive. They are generally believed to represent key structural components of large-scale F-actin cohesion in cells required for cell shape and motility. α-Actinin-2 has been implicated in myopathies such as nemalin body myopathy, hypertrophic and dilated cardiomyopathy and it may have at least an indirect pathogenetic role in diseases of the central nervous system (CNS) like schizophrenia, epilepsy, ischemic brain damage, CNS lupus and neurodegenerative disorders. The role of "non-muscle" α-actinins in the kidney seems to be crucial as an essential component of the glomerular filtration barrier. Therefore, they have been implicated in the pathogenesis of familial focal segmental glomerulosclerosis, nephrotic syndrome, IgA nephropathy, focal segmental glomerulosclerosis and minimal change disease. α-Actinin is also expressed on the membrane and cytosol of parenchymal and ductal cells of the liver and it seems that it interacts with hepatitis C virus in an essential way for the replication of the virus. Finally α-actinin, especially α-actinin-4, has been implicated in cancer cell progression and metastasis, as well as the migration of several cell types participating in the immune response. Based on these functions, the accumulating reported evidence of the importance of α-actinin as a target autoantigen in the pathogenesis of autoimmune diseases, particularly systemic lupus erythematosus and autoimmune hepatitis, is also discussed along with the possible perspectives that are potentially emerging from the study of this peculiar molecule in health and disease. © 2011 Elsevier B.V.
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Double reactivity against actin and alpha-actinin defines a severe form of autoimmune hepatitis type 1 Gueguen, P.; Dalekos, G.; Nousbaum, J. B.; Zachou, K.; Putterman, C.; Youinou, P.; Renaudineau, Y. (2006)Anti-filamentous actin antibodies characterize autoimmune hepatitis type 1 (AIH-1). Recently, the binding domain of alpha-actinin on actin was shown to be a predominant epitope. To test this reactivity, an anti-alpha-actinin ...
Anti-alpha-actinin antibodies cross-react with Anti-ssDNA antibodies in active autoimmune hepatitis Renaudineau, Y.; Dalekos, G. N.; Gueguen, P.; Zachou, K.; Youinou, P. (2008)Recently, we have observed that the association of anti-F-actin autoantibodies (Abs) with anti-alpha-actinin Abs (double reactivity) was correlated with liver disease activity in autoimmune hepatitis type 1 (AIH-1; Gueguen ...
Clinical significance of organ- and non-organ-specific autoantibodies on the response to anti-viral treatment of patients with chronic hepatitis C Gatselis, N. K.; Georgiadou, S. P.; Koukoulis, G. K.; Tassopoulos, N.; Zachou, K.; Liaskos, C.; Hatzakis, A.; Dalekos, G. N. (2006)Background: Development of organ- and non-organ-specific autoantibodies has been reported in hepatitis C virus patients treated with interferon-α plus/minus ribavirin. Aims: To address whether prevalence and the titre of ...