activity-dependent subcellular cotrafficking of the small gtpase rem2 and ca2+cam-dependent protein kinase iiα活动依赖性小的亚细胞cotrafficking gtpase rem2和ca2 + cam-dependent蛋白激酶iiα.pdfVIP

Activity-Dependent Subcellular Cotrafficking of the Small GTPase Rem2 and Ca2+/CaM-Dependent Protein Kinase IIa 1 2 2 1 2,3 Robyn Flynn , Etienne Labrie-Dion , Nikolas Bernier , Michael A. Colicos , Paul De Koninck , Gerald W. Zamponi1* 1 Department of Physiology and Pharmacology, Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada, 2 Centre de Recherche de l’Institut universitaire ´ ´ ´ ´ ´ ´ ´ ´ en sante mentale de Quebec, Quebec City, Quebec, Canada, 3 Departement de Biochimie, Microbiologie et Bio-Informatique, Universite Laval, Quebec City, Quebec, Canada Abstract Background: Rem2 is a small monomeric GTP-binding protein of the RGK family, whose known functions are modulation of calcium channel currents and alterations of cytoskeletal architecture. Rem2 is the only RGK protein found predominantly in the brain, where it has been linked to synaptic development. We wished to determine the effect of neuronal activity on the subcellular distribution of Rem2 and its interacting partners. Results: We show that Rem2 undergoes activity-and N-Methyl-D-Aspartate Receptor (NMDAR)-dependent translocation in rat hippocampal neurons. This redistribution of Rem2, from a diffuse pattern to one that is highly punctate, is dependent on Ca2+ influx, on binding to calmodulin (CaM), and also involves an auto-inhibitory domain within the Rem2 distal C-terminus region. We found that Rem2 can bind to Ca2+/CaM-dependent protein kinase IIa (CaMKII) a in Ca2+/CaM-dependent manner. Furthermore, our data reveal a spatial and temporal correlation betwe