Myospryn is a novel binding partner for dysbindin in muscle.
Dysbindin is a coiled-coil-containing protein that was initially identified in a screen for dystrobrevin-interacting proteins. Recently, dysbindin has been shown to be involved in the biogenesis of lysosome-related organelles and is also a major schizophrenia susceptibility factor. Although dysbindin has been implicated in a number of different cellular processes, little is known about its function. To determine the function of dysbindin in muscle, we performed a yeast two-hybrid screen to identify potential interacting proteins. Here we show that dysbindin binds to a novel 413-kDa protein, myospryn, which is expressed in cardiac and skeletal muscle. The transcript encoding myospryn encompasses genethonin-3, a transcript that is down-regulated in muscle from Duchenne muscular dystrophy patients and stretch-responsive protein 553, which is up-regulated in experimental muscle hypertrophy. The C terminus of myospryn contains BBC, FN3, and SPRY domains in a configuration reminiscent of the tripartite motif protein family, as well as the dysbindin-binding site and a region mediating self-association. Dysbindin and myospryn co-immunoprecipitate from muscle extracts and are extensively co-localized. These data demonstrate for the first time that there are tissue-specific ligands for dysbindin that may play important roles in the different disease states involving this protein.
Benson
Matthew A
MA
Department of Pharmacology, University of Oxford, United Kingdom.
Tinsley
Caroline L
CL
Blake
Derek J
DJ
D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology*; D018076:DNA, Complementary / Q000378:metabolism; D015536:Down-Regulation; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology*; D009132:Muscles / Q000378:metabolism*; D011233:Precipitin Tests; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013347:Subcellular Fractions / Q000378:metabolism; D014018:Tissue Distribution; D014162:Transfection; D020798:Two-Hybrid System Techniques; D015854:Up-Regulation; D001616:beta-Galactosidase / Q000378:metabolism
D002352:Carrier Proteins; C484938:Cmya5 protein, mouse; D018076:DNA, Complementary; C498992:Dtnbp1 protein, mouse; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009124:Muscle Proteins; D012333:RNA, Messenger; C484939:genethonin-3 protein, mouse; D001616:beta-Galactosidase