14-3-3-PROTEINS IN NEURONAL DEVELOPMENT AND FUNCTION

The 14-3-3 proteins are small, cytosolic, evolutionarily conserved pro teins expressed abundantly in the nervous system. Although they were d iscovered more than 30 yr ago, their function in the nervous system ha s remained enigmatic. Several recent studies have helped to clarify th eir biological function. Crystallographic investigations have revealed that 14-3-3 proteins exist as dimers and that they contain a specific region for binding to other proteins. The interacting proteins, in tu rn, contain a 14-3-3 binding motif; proteins that interact with 14-3-3 dimers include PKC and Raf, protein kinases with critical roles in ne uronal signaling. These proteins are capable of activating Raf in vitr o, and this role has been verified by in vivo studies in Drosophila. M ost interestingly, mutations in the Drosophila 14-3-3 genes disrupt ne uronal differentiation, synaptic plasticity, and behavioral plasticity , establishing a role for these proteins in the development and functi on of the nervous system.