Institute of Biomedical Research and Technology, Centre for Research and Technology-Thessaly, Larissa, Greece.
Autoimmun Rev. 2011 May;10(7):389-96. doi: 10.1016/j.autrev.2010.12.009. Epub 2011 Jan 15.
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.
α-辅肌动蛋白（α-actinin）是一种普遍存在的细胞骨架蛋白，属于丝状肌动蛋白（F-actin）交联蛋白超家族。它存在于肌肉和非肌肉细胞的多个亚细胞区域，包括细胞-细胞和细胞-基质接触部位、细胞突起和应力纤维密集区，因此，它似乎通过将细胞骨架与各种连接点的许多不同跨膜蛋白连接起来，在细胞中发挥多种重要作用。目前已经鉴定出四种人类α-辅肌动蛋白同工型，即“肌肉”α-辅肌动蛋白-2 和 α-辅肌动蛋白-3，以及“非肌肉”α-辅肌动蛋白-1 和 α-辅肌动蛋白-4。α-辅肌动蛋白同工型的确切功能以及它们与 F-actin 的结合在体内的精确作用和意义一直难以捉摸。人们普遍认为，它们代表了细胞中大规模 F-actin 凝聚的关键结构成分，对于细胞形状和运动至关重要。α-辅肌动蛋白-2 与 nemalin 体肌病、肥厚性和扩张性心肌病有关，它可能在中枢神经系统（CNS）疾病如精神分裂症、癫痫、缺血性脑损伤、CNS 狼疮和神经退行性疾病中具有至少间接的致病作用。“非肌肉”α-辅肌动蛋白在肾脏中的作用似乎至关重要，因为它是肾小球滤过屏障的重要组成部分。因此，它们与家族性局灶节段性肾小球硬化症、肾病综合征、IgA 肾病、局灶节段性肾小球硬化症和微小病变性疾病的发病机制有关。α-辅肌动蛋白也在肝脏的实质细胞和胆管细胞的膜和细胞质中表达，并且它似乎与丙型肝炎病毒以一种至关重要的方式相互作用，以促进病毒的复制。最后，α-辅肌动蛋白，特别是 α-辅肌动蛋白-4，与癌细胞的进展和转移以及参与免疫反应的几种细胞类型的迁移有关。基于这些功能，还讨论了积累的证据表明α-辅肌动蛋白作为自身免疫疾病发病机制中的靶自身抗原的重要性，特别是系统性红斑狼疮和自身免疫性肝炎，以及从研究这种特殊分子在健康和疾病中可能出现的潜在观点。
