Identification of a repeated domain within mammalian alpha-synemin that interacts directly with talin.
The type VI intermediate filament (IF) protein synemin is a unique member of the IF protein superfamily. Synemin associates with the major type III IF protein desmin forming heteropolymeric intermediate filaments (IFs) within developed mammalian striated muscle cells. These IFs encircle and link all adjacent myofibrils together at their Z-lines, as well as link the Z-lines of the peripheral layer of cellular myofibrils to the costameres located periodically along and subjacent to the sarcolemma. Costameres are multi-protein assemblies enriched in the cytoskeletal proteins vinculin, alpha-actinin, and talin. We report herein a direct interaction of human alpha-synemin with the cytoskeletal protein talin by protein-protein interaction assays. The 312 amino acid insert (SNTIII) present only within alpha-synemin binds to the rod domain of talin in vitro and co-localizes with talin at focal adhesion sites within mammalian muscle cells. Confocal microscopy studies showed that synemin co-localizes with talin within the costameres of human skeletal muscle cells. Analysis of the primary sequences of human alpha- and beta-synemins revealed that SNTIII is composed of seven tandem repeats, each containing a specific Ser/Thr-X-Arg-His/Gln (S/T-X-R-H/Q) motif. Our results suggest human alpha-synemin plays an essential role in linking the heteropolymeric IFs to adherens-type junctions, such as the costameres within mammalian striated muscle cells, via its interaction with talin, thereby helping provide mechanical integration for the muscle cell cytoskeleton.
Sun
Ning
N
Muscle Biology Group, Department of Biochemistry, Biophysics, and Molecular Biology, Iowa State University, Ames, IA 50011-3260, USA.
Critchley
David R
DR
Paulin
Denise
D
Li
Zhenlin
Z
Robson
Richard M
RM
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D002460:Cell Line; D006801:Humans; D007381:Intermediate Filament Proteins / Q000032:analysis / Q000737:chemistry* / Q000378:metabolism; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000737:chemistry* / Q000166:cytology; D017434:Protein Structure, Tertiary; D051381:Rats; D020449:Repetitive Sequences, Amino Acid; D012508:Sarcolemma / Q000737:chemistry; D012518:Sarcomeres / Q000737:chemistry; D017386:Sequence Homology, Amino Acid; D016608:Talin / Q000032:analysis / Q000737:chemistry* / Q000378:metabolism; D016596:Vinculin / Q000378:metabolism
D007381:Intermediate Filament Proteins; D016608:Talin; C430456:desmuslin; D016596:Vinculin