Alpha-actinin: A multidisciplinary protein with important role in B-cell driven autoimmunity

作者：Oikonomou Katerina G; Zachou Kalliopi; Dalekos George N^*

来源：Autoimmunity Reviews, 2011, 10(7): 389-396.

DOI：10.1016/j.autrev.2010.12.009

• alpha-Actinin
• Filamentous actin
• Smooth muscle autoantibodies
• Systemic lupus etythematosus
• Autoimmune hepatitis
• Lupus nephritis
• Liver autoimmunity

Alpha-actinin (alpha-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 alpha-actinin have already been identified namely, the "muscles" alpha-actinin-2 and alpha-actinin-3 and the "non-muscles" alpha-actinin-1 and alpha-actinin-4. The precise functions of alpha-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. alpha-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" alpha-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. alpha-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 alpha-actinin, especially alpha-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 alpha-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.

• 出版日期2011-5