The mechanism of the neurotransmitter release in growth cones

The growth cone is considered the precursor of the presynaptic terminal. To elucidate the minimal molecular machinery required for exocytosis, we exam ined the characteristics of ol-latrotoxin-induced exocytosis in growth cone s. In isolated growth cones (IGC), neurotransmitters were released in a SNA RE-dependent manner, but rab3A cycling was blocked. By supplying rabphilin, a rab3A acceptor found in low levels in IGC, the IGC obtained as high an e xocytotic efficiency as adult synaptosomes, and the complete GDP-GTP conver sion of rab3A occurred on growth cone vesicles (GCV). GCVs bound SNAREs but not NSF or alpha-SNAP; whereas in the rabphilin-supplied IGC, GCVs recruit ed both NSF and alpha-SNAP, to form the SNARE-NSF-SNAP complex. These resul ts suggest that rab3A cycling is dependent upon the accumulation of rabphil in and is completed later than the SNARE mechanism, and that rabphilin is i nvolved in determining the efficiency of exocytosis by modifying the SNARE mechanism. J. Neurosci. Res. 60:743-753, 2000. (C) 2000 Wiley-Liss, Inc.