Synip: A novel insulin-regulated syntaxin 4-binding protein mediating GLUT4 translocation in adipocytes

Insulin-stimulated glucose transport and GLUT4 translocation require regula ted interactions between the v-SNARE, VAMP2, and the t-SNARE, syntaxin 4. W e have isolated a novel syntaxin 4-binding protein, Synip, which specifical ly interacts with syntaxin 4. Insulin induces a dissociation of the Synip:s yntaxin 4 complex due to an apparent decrease in the binding affinity of Sy nip for syntaxin 4. In contrast, the carboxyterminal domain of Synip does n ot dissociate from syntaxin 4 in response to insulin stimulation but inhibi ts glucose transport and GLUT4 translocation. These data implicate Synip as an insulin-regulated syntaxin 4-binding protein directly involved in the c ontrol of glucose transport and GLUT4 vesicle translocation.