Physical and functional interaction of rabphilin-3A with α-actinin

Abstract

Rabphilin-3A is a downstream target molecule of Rab3A small GTP-binding protein and implicated in Ca2+-dependent neurotransmitter release. Here we have isolated a rabphilin-3A-interacting molecule from a human brain cDNA library by the yeast two-hybrid method and identified it to be α-actinin, known to cross-link actin filaments into a bundle. α-Actinin interacts with the N-terminal region of rabphilin-3A, with which GTP-Rab3A interacts, and this interaction stimulates the activity of α-actinin to cross-link actin filaments into a bundle. The interaction of rabphilin-3A with α-actinin is inhibited by guanosine 5'-(3-O-thio)triphosphate-Rab3A. These results suggest that the Rab3A-rabphilin-3A system regulates the α-actinin-regulated reorganization of actin filaments. It has been shown that reorganization of actin filaments is also involved in Ca2+ dependent exocytosis. Therefore, rabphilin-3A may serve as a linker for Rab3A and cytoskeleton.