A NOVEL CALMODULIN-BINDING PROTEIN, BELONGING TO THE WD-REPEAT FAMILY, IS LOCALIZED IN DENDRITES OF A SUBSET OF CNS NEURONS

A rat brain synaptosomal protein of 110,000 M(r) present in a fraction highly enriched in adenylyl cyclase activity was microsequenced (Cast ets, F., G. Baillat, S. Mirzoeva, K. Mabrouk, J. Garin, J. d'Alayer, a nd A. Monneron. 1994. Biochemistry. 33:5063-5069). Peptide sequences w ere used to clone a cDNA encoding a novel, 780-amino acid protein name d striatin. Striatin is a member of the WD-repeat family (Neer, E.J., C.J. Schmidt, R. Nambudripad, and T.F. Smith. 1994, Nature (Lend.). 37 1:297-300), the first one known to bind calmodulin (CaM) in the presen ce of Ca++. Subcellular fractionation shows that striatin is a membran e-associated, Lubrol-soluble protein. As analyzed by Northern blots, i n situ hybridization, and immunocytochemistry, striatin is localized i n the central nervous system, where it is confined to a subset of neur ons, many of which are associated with the motor system. In particular , striatin is conspicuous in the dorsal part of the striatum, as well as in motoneurons. Furthermore, striatin is essentially found in dendr ites, but not in axons, and is most abundant in dendritic spines. We p ropose that striatin interacts, through its WD-repeat domain and in a CaM/Ca++-dependent manner, with one or several members of a surroundin g cluster of molecules engaged in a Ca++-signaling pathway specific to excitatory synapses.