Rabphilin-3A is a downstream target molecule of Rab3A small GTP-binding protein and implicated in Ca 2؉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 ␣-actinin, known to cross-link actin filaments into a bundle. ␣-Actinin interacts with the N-terminal region of rabphilin-3A, with which GTP- Rab3A interacts, and this interaction stimulates the activity of

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... to cross-link actin filaments into a bundle. The interaction of rabphilin-3A with ␣-actinin is inhibited by guanosine 5-(3-O-thio)triphosphate- Rab3A. These results suggest that the Rab3A-rabphilin-3A system regulates the ␣-actinin-regulated reorganization of actin filaments. It has been shown that reorganization of actin filaments is also involved in Ca 2؉dependent exocytosis. Therefore, rabphilin-3A may serve as a linker for Rab3A and cytoskeleton.