Human alpha-synemin interacts directly with vinculin and metavinculin.
Synemin is a very large, unique member of the IF (intermediate filament) protein superfamily. Association of synemin with the major IF proteins, desmin and/or vimentin, within muscle cells forms heteropolymeric IFs. We have previously identified interactions of avian synemin with alpha-actinin and vinculin. Avian synemin, however, is expressed as only one form, whereas human synemin is expressed as two major splice variants, namely alpha- and beta-synemins. The larger alpha-synemin contains an additional 312-amino-acid insert (termed SNTIII) located near the end of the long C-terminal tail domain. Whether alpha- and beta-synemins have different cellular functions is unclear. In the present study we show, by in vitro protein-protein interaction assays, that SNTIII interacts directly with both vinculin and metavinculin. Furthermore, SNTIII interacts with vinculin in vivo, and this association is promoted by PtdIns(4,5)P(2). SNTIII also specifically co-localizes with vinculin within focal adhesions when transiently expressed in mammalian cells. In contrast, other regions of synemin show distinct localization patterns in comparison with those of SNTIII, without labelling focal adhesions. Our results indicate that alpha-synemin, but not beta-synemin, interacts with both vinculin and metavinculin, thereby linking the heteropolymeric IFs to adhesion-type junctions, such as the costameres located within human striated muscle cells.
Sun
Ning
N
Muscle Biology Group, Department of Biochemistry, Biophysics and Molecular Biology and of Animal Science, Iowa State University, Ames, IA 50011-3260, USA.
Critchley
David R
DR
Paulin
Denise
D
Li
Zhenlin
Z
Robson
Richard M
RM
D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D022001:Focal Adhesions; D006801:Humans; D007381:Intermediate Filament Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018482:Muscle, Skeletal / Q000378:metabolism; D011485:Protein Binding; D051381:Rats; D014746:Vimentin / Q000235:genetics / Q000378:metabolism; D016596:Vinculin / Q000378:metabolism*
D007381:Intermediate Filament Proteins; D014746:Vimentin; C430456:desmuslin; C103334:metavinculin; D016596:Vinculin