Cloning and characterization of a novel RING finger protein that interactswith class V myosins

We have identified a novel protein (BERP) that is a specific partner for th e tail domain of myosin V, Class V myosins are a family of molecular motors thought to interact via their unique C-terminal tails with specific protei ns for the targeted transport of organelles. BERP is highly expressed in br ain and contains an N-terminal RING finger, Followed by a B-box zinc finger , a coiled-coil (RBCC domain), and a unique C-terminal beta-propeller domai n. A yeast two-hybrid screening indicated that the C-terminal beta-propelle r domain mediates binding to the tail of the class V myosin myr6 (myosin Vb ), This interaction was confirmed by immunoprecipitation, which also demons trated that BERP could associate with myosin Va, the product of the dilute gene. Like myosin Va, BERP is expressed in a punctate pattern in the cytopl asm as well as in the neurites and growth cones of PC12 cells. We also foun d that the RBCC domain of BERP is involved in protein dimerization. Stable expression of a mutant form of BERP lacking the myosin-binding domain but c ontaining the dimerization domain resulted in defective PC12 cell spreading and prevented neurite outgrowth in response to nerve growth factor. Our st udies present a novel interaction for the beta-propeller domain and provide evidence for a role for BERP in myosin V-mediated cargo transport.