β2-syntrophin is a cdk5 substrate that restrains the motility of insulin secretory granulesβ2-syntrophin cdk5衬底,抑制胰岛素分泌颗粒的能动性.pdfVIP

b2-Syntrophin Is a Cdk5 Substrate That Restrains the Motility of Insulin Secretory Granules 1,2 1 1 3 2 Sandra Schubert , Klaus-Peter Knoch , Joke Ouwendijk , Shabaz Mohammed , Yury Bodrov , Melanie ¨ 1 ¨ 1 1,2 4 5 4 Jager , Anke Altkruger , Carolin Wegbrod , Marvin E. Adams , Yong Kim , Stanley C. Froehner , Ole N. Jensen3, Yannis Kalaidzidis2,6, Michele Solimena1,2* 1 Molecular Diabetology, Paul Langerhans Institute Dresden, Uniklinikum Carl Gustav Carus at Dresden University of Technology, Dresden, Germany, 2 Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany, 3 Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark, 4 Department of Physiology and Biophysics, University of Washington, Seattle, Washington, United States of America, 5 Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, New York, United States of America, 6 A. N. Belozersky Institute of Physico-Chemical Biology, Moscow State University, Moscow, Russia Abstract The molecular basis for the interaction of insulin granules with the cortical cytoskeleton of pancreatic b-cells remains unknown. We have proposed that binding of the granule protein ICA512 to the PDZ domain of b2-syntrophin anchors granules to actin filaments and that the phosphorylation/dephosphorylation of b2-syntrophin regulates this association. Here we tested this hypothesis by analyzing INS-1 cells expressing GFP-b2-syntrophin through the combined