Expression of the intermediate filament protein synemin in myofibrillar myopathies and other muscle diseases.
Synemin is a member of the intermediate protein superfamily. Previous studies in avian and rodent skeletal and cardiac muscles have demonstrated that synemin localises at the Z-band, where it associates with desmin and alpha-actinin. In the present study, the distribution of synemin was examined using immunohistochemistry in muscle biopsy specimens from patients suffering from myofibrillar myopathy (MM, n=6), dermatomyositis (DM, n=3), inclusion body myositis (IBM, n=5), oculopharyngeal muscular dystrophy (OPD, n=3) and denervation atrophy (DA, n=3), to investigate the possible participation of this protein in the pathogenesis of various muscular diseases. Of patients affected by MM, two showed the presence of mutations in the desmin gene; none had mutations in the alphaB-crystallin gene; and no mutations were identified in synemin or syncoilin genes of three patients. Synemin immunohistochemistry disclosed a faint staining corresponding to the Z-bands in the cytoplasm of control muscle fibres; in contrast, focal aggregates of synemin were seen in patients with MM. Increased synemin immunoreactivity was identified diffusely or in the subsarcolemmal space of scattered fibres in patients with DM, and in vacuolated fibres of patients with IBM and OPD. Strong synemin immunoreactivity was observed in target formations and atrophic fibres of patients with denervating disorders, as well as in atrophic fibres, regardless of their origin, in all patients studied. Synemin co-localised with desmin, as seen on consecutive serial sections immunostained with anti-synemin or anti-desmin antibodies. These observations demonstrate abnormal accumulations containing both synemin and desmin in muscle fibres in patients with MM, IBM, DM, OPD and DA. Considering the important role of synemin as one of intermediate filaments of skeletal and cardiac muscle, its destruction and accumulation in the intracellular debris suggest that synemin may participate in the pathogenesis of these disorders.
Olivé
Montse
M
Institut de Neuropatologia, Ciutat Sanitària i Universitària de Bellvitge, C/Feixa Llarga s/n masculine, 08907 Hospitalet de Llobregat, Spain. 25169mop@comb.es
Goldfarb
Lev
L
Dagvadorj
Ayush
A
Sambuughin
Nyamkhishig
N
Paulin
Denise
D
Li
Zhenlin
Z
Goudeau
Bertrand
B
Vicart
Patrick
P
Ferrer
Isidro
I
D000328:Adult; D000368:Aged; D003893:Desmin / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D002479:Inclusion Bodies / Q000378:metabolism / Q000473:pathology; D007381:Intermediate Filament Proteins; D008297:Male; D008875:Middle Aged; D018485:Muscle Fibers, Skeletal / Q000378:metabolism / Q000473:pathology; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D009135:Muscular Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009154:Mutation
D003893:Desmin; D007381:Intermediate Filament Proteins; D009124:Muscle Proteins; C430456:desmuslin