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.