Sarcoglycan subcomplex: state of the art

摘要

More than 15 years have elapsed since the discovery of the sarcoglycan complex (SGC) [1] and the characteristics of this original complex have been fairly studied in succeeding years later [2]. In details, sarcoglycan (SG) is a component of the larger dystrophin-associated glycoproteins complex (DAGC) called DGC also [1]. The DAGC is composed of at least ten proteins links laminin2 (merosin) of the extracellular matrix and actin, stabilizing the cell membrane during muscle activity. Three subcomplex can be identified in the DAGC on the basis of different biochemical characteristic and localization: the sarcoplasmic subcomplex, made up of the dystrophin, dystrobrevin and syntrophin complex; the dystroglycan subcomplex, made up of a- and b-dystroglycan; the SGC, composed of six SG subunits (a, b, g, d, e and z-SG). SGC subcomplex is an independent complex that is not directly associated with dystrophin and it plays a key role in signalling functions maintaining sarcolemma viability in muscle fiber membrane. As mutations in any one of SG subunits cause autosomal recessive limb-girdle muscular dystrophy (LGMD), characterized by integrity of dystrophin, SGC can be considered as associated system of DAGC and for this, it seems to be functionally as important as dystrophin. Moreover, previous reports have demonstrated that SGs are localized in skeletal and cardiac muscle forming the costameres, also showing that these proteins are co-localized with integrins in these regions in skeletal muscle in the region of the sarcolemma over I or A bands on the basis of the fiber types, slow or fast respectively [3,4]. These results have reinforced the hypothesis of a functional connection between SGs and integrins through a bidirectional signalling [5] which seems to be important to alleviate muscle diseases and to improve the survival of a severely dystrophic mouse model of Duchenne muscular dystrophy. For this, in our opinion the study of SGs implies also the consequent analysis of the integrins in many different tissues. Furthermore, it was demonstrated the presence of all SGs, and then of an exameric arrangement of SGC, in smooth muscle fibers of many districts [6,7] emphasizing an important correlation between SGs and frequency of contraction force [7,8]. Whereas the expression of a and g-SG is restricted to striated muscle cells, the other SGs are widely expressed in various tissues as levels of b, d and e-SG were highest in lung, moderate in brain, heart, and low, but detectable in kidney and liver [9]. Then, since this complex is not considered as muscle-specific, previously we have analyzed the SGs in non-muscle tissues, as well as digestive, respiratory and urinary epithelial cells. Interestingly, our immunohistochemical results showed the presence of all SGs in all tested tissues. About this, recently, we analyzed SGC in biopsies obtained from human breast and prostate in normal and pathological conditions in order to study these proteins also in glandular epithelium. Our results showed, for the first time, that in normal conditions, staining pattern for all SGs has been detectable and distributed in both epithelial and myoepithelial cells. Moreover, observations on samples of pathological tissues have shown that immunofluorescence for all SGs appears to be severely reduced in benign diseases, and almost absent in malignant syndromes. These results were confirmed also by data obtained on gingival epithelium in normal and pathological conditions. Particularly, our results on normal gingival epithelium showed the presence of SGC in this tissue confirming that SGs are ubiquitously distributed; in gingival epithelium, obtained from patients during inflammatory processes, due to treatment with bisphosphonates, staining pattern for SGs was decreased. Then, SGs could play a crucial role in oncogenesis since it is possible to hypothesize that these diseases could be due to lack of SGs in epithelial cells; moreover, the invasivity of malignan