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 Mr present in a fraction highly enriched in adenylyl cy- clase activity was microsequenced (Castets, F., G. Bail- lat, S. Mirzoeva, K. Mabrouk, J. Garin, J. d'Alayer, and A. Monneron. 1994. Biochemistry. 33:5063-5069). Pep- tide sequences were used to clone a cDNA encoding a novel, 780-amino acid protein named striatin. Striatin is a member of the WD-repeat family (Neer, E.J., C.J. Schmidt, R. Nambudripad, and T.F. Smith. 1994. Na- ture (Lond.). 371:297-300), the first one known to bind calmodulin (CAM) in the presence of Ca + ÷. Subcellular fractionation shows that striatin is a membrane-associ- ated, Lubrol-soluble protein. As analyzed by Northern blots, in situ hybridization, and immunocytochemistry, striatin is localized in the central nervous system, where it is confined to a subset of neurons, 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 dendrites, but not in axons, and is most abun- dant in dendritic spines. We propose that striatin inter- acts, through its WD-repeat domain and in a CaM/ Ca + +-dependent manner, with one or several members of a surrounding cluster of molecules engaged in a Ca + +-signaling pathway specific to excitatory synapses.