Immunohistochemical and molecular study of sarcoglycan subcomplex in normal human smooth muscle

The evidence that sarcoglycans seem to be functionally and pathologically important as dystrophin, it has permitted to study these transmembrane proteins more attentively, and in last years numerous studies have been carried out on sarcoglycan subcomplex in smooth muscle.This subcomplex consists of four transmembrane proteins, -, -, -, and -sarcoglycan.The synthesis of all four of the sarcoglycans is required to ensure the proper localization of the complex to the cell surface membrane; 1 then the complex formation and the localization of sarcoglycan subcomplex require all four subunits since that the direct interaction beteewen the sarcoglycans has been demonstrated biochemically by co-immunoprecipitation.2 A fifth sarcoglycan homologous to -sarcoglycan, -sarcoglycan, is more broadly expressed, showing a wider tissue distribution, also in non-muscle tissues.3 Previous observations demonstrated that in lung, this glycoprotein was associated with both alveoli and bronchioles and that the sections of urogenital and digestive tracts were -sarcoglycan positive.3 Recently, a novel mammalian sarcoglycan, -sarcoglycan, has been identified and it is a protein highly related to - and -sarcoglycan mediating membrane stability together other sarcoglycans. Numerous studies have demonstrated that all sarcoglycans can be organized in various subcomplexes but only common assumption of them is a tetramerix arrangement of sarcoglycan sub complex. On this starting point, in our recent immunohistochemical investivgation, carried out on surgical biopsies of human adult visceral smooth muscle, we showed that all sarcoglycans coexist in the same fiber, hypothesizing the presence of pentameric structure.4 Addressing this issue, in the present work we extend our previous results, with immunofluorescence and molecular techniques, testing all districts of human body (gastroenteric, respiratory, vascular and urogenital tracts) in order to better verify the real arrangement of sarcoglycan subcomplex. Our results, that show the constant presence of all sarcoglycan in all districts, confirm a real pentameric, or considering -sarcoglycan detected with rt-PCR, hexameric model of sarcoglycan subcomplex. This hypothetic new complex, formed by all sarcoglycans, could present a higher or lower expression of single sarcoglycan in conformity with muscle type, skeletal, cardiac, or smooth, or also in conformity with the origin of smooth muscle, gastrointestinal, urogenital, or respiratory tract. References 1. Holt KH, Campbell KP Assembly of the sarcoglycan complex. Insights for muscular dystrophy. J Biol Chem 1998;273:34667-70 2. Yoshida M et al., Dissociation of the complex of dystrophin and its associated proteins into several unique groups by n-octyl -D-glucoside. Eur J Biochem 1994;222:1055-61. 3. Ettinger AJ et al., e-sarcoglycan, a broadly expressed homologue of the gene mutated in limb-girdle muscular dystrophy 2D. J Biol Chem 1997;272:32534-8. 4. Anastasi G et al, Sarcoglycan subcomplex in normal human smooth muscle: an immunohistochemical and molecular study. Int J Mol Med. 2005;16:367-74.