Anastasi Giuseppe, Cutroneo Giuseppina, Trimarchi Fabio, Santoro Giuseppe, Bruschetta Daniele, Bramanti Placido, Pisani Antonina, Favaloro Angelo
Department of Biomorphology and Biotechnologies, Policlinico Universitario 'G. Martino', University of Messina, I-98125 Messina, Italy.
Int J Mol Med. 2004 Dec;14(6):989-99.
The sarcoglycan subcomplex (SGC) is a well-known system of interaction between extracellular matrix and sarcolemma-associated cytoskeleton in skeletal and cardiac muscle. The SGC is included in the DGC made up of sarcoplasmic subcomplex and a dystroglycan subcomplex. Recent developments in molecular genetics have demonstrated that the mutation of each single sarcoglycan gene, causes a series of recessive autosomal muscular dystrophies, dystrophin-positive, called sarcoglycanopathies or limb girdle muscular dystrophies. Our recent studies have demonstrated that costameres are a proteic machinery made up of DGC and vinculin-talin-integrin system, also revealing the colocalization of sarcoglycans and integrins in adult human skeletal muscle. These results may support the hypothesis of the existence of a bidirectional signalling between sarcoglycans and integrins in cultured L6 myocytes. The hypothesis of bidirectional signalling between sarcoglycans and integrins could be supported by the identification of a skeletal and cardiac muscle filamin2 as a gamma-sarcoglycan, delta-sarcoglycan and, hypothetically, beta1 integrin interacting protein. Our results, acquired with an immunofluorescence study on adult human skeletal muscle affected by LGMD type 2D and 2C, showed that in LGMD2D: a) alpha-sarcoglycan staining is severely reduced; b) the beta-gamma-delta-sarcoglycan subunit and all tested integrins staining are clearly detectable; c) filamin2 is normal and shows a costameric distribution. In LGMD2C: a) alpha-sarcoglycan staining is preserved; b) the beta-gamma-delta-sarcoglycan subunit staining is severely reduced; c) the alpha7B-integrin is slightly reduced and beta1D-integrin is severely reduced; d) filamin2 is severely reduced. Other tested proteins of the two systems show a normal staining pattern in both sarcoglycanopathies. Our study seems to confirm, for the first time on adult human skeletal muscle of subjects affected by LGMDs, the hypo-theses of: a) the existence, in mouse myotubes in culture, of two distinct subunits in sarcoglycans subcomplex; b) the presence of a bidirectional signalling between sarcoglycans and integrins, previously demonstrated on rat cultured L6 myocytes; c) the interaction of FLN2 with both sarcoglycans and integrins. These results may stimulate the search of yet unidentified common interactors of both fiber-extracellular matrix interaction systems.
肌聚糖亚复合物（SGC）是骨骼肌和心肌中细胞外基质与肌膜相关细胞骨架之间一个著名的相互作用系统。SGC包含在由肌浆亚复合物和肌营养不良聚糖亚复合物组成的DGC中。分子遗传学的最新进展表明，每个单一肌聚糖基因突变都会导致一系列隐性常染色体肌营养不良症，即肌营养不良蛋白阳性的肌聚糖病或肢带型肌营养不良症。我们最近的研究表明，肌小节是由DGC和纽蛋白-踝蛋白-整合素系统组成的蛋白质机器，同时也揭示了肌聚糖和整合素在成人骨骼肌中的共定位。这些结果可能支持在培养的L6肌细胞中肌聚糖和整合素之间存在双向信号传导的假说。骨骼肌和心肌细丝蛋白2被鉴定为γ-肌聚糖、δ-肌聚糖以及假设的β1整合素相互作用蛋白，这可能支持肌聚糖和整合素之间双向信号传导的假说。我们通过对受2D型和2C型肢带型肌营养不良症影响的成人骨骼肌进行免疫荧光研究获得的结果表明，在2D型肢带型肌营养不良症中：a）α-肌聚糖染色严重减少；b）β-γ-δ-肌聚糖亚基和所有测试的整合素染色均可清晰检测到；c）细丝蛋白2正常且呈肌小节分布。在2C型肢带型肌营养不良症中：a）α-肌聚糖染色保留；b）β-γ-δ-肌聚糖亚基染色严重减少；c）α7B整合素略有减少，β1D整合素严重减少；d）细丝蛋白2严重减少。在这两种肌聚糖病中，两个系统的其他测试蛋白均显示正常的染色模式。我们的研究似乎首次在受肢带型肌营养不良症影响的成人骨骼肌中证实了以下假说：a）在培养的小鼠肌管中，肌聚糖亚复合物存在两个不同的亚基；b）肌聚糖和整合素之间存在双向信号传导，这一点先前已在大鼠培养的L6肌细胞中得到证实；c）FLN2与肌聚糖和整合素均有相互作用。这些结果可能会促使人们寻找这两个纤维-细胞外基质相互作用系统中尚未确定的共同相互作用分子。
