Abstract：
:The molecular organization of presynaptic active zones is important for the neurotransmitter release that is triggered by depolarization-induced Ca2+ influx. Here, we demonstrate a previously unknown interaction between two components of the presynaptic active zone, RIM1 and voltage-dependent Ca2+ channels (VDCCs), that controls neurotransmitter release in mammalian neurons. RIM1 associated with VDCC beta-subunits via its C terminus to markedly suppress voltage-dependent inactivation among different neuronal VDCCs. Consistently, in pheochromocytoma neuroendocrine PC12 cells, acetylcholine release was significantly potentiated by the full-length and C-terminal RIM1 constructs, but membrane docking of vesicles was enhanced only by the full-length RIM1. The beta construct beta-AID dominant negative, which disrupts the RIM1-beta association, accelerated the inactivation of native VDCC currents, suppressed vesicle docking and acetylcholine release in PC12 cells, and inhibited glutamate release in cultured cerebellar neurons. Thus, RIM1 association with beta in the presynaptic active zone supports release via two distinct mechanisms: sustaining Ca2+ influx through inhibition of channel inactivation, and anchoring neurotransmitter-containing vesicles in the vicinity of VDCCs.
journal_name
Nat Neuroscijournal_title
Nature neuroscienceauthors
Kiyonaka S,Wakamori M,Miki T,Uriu Y,Nonaka M,Bito H,Beedle AM,Mori E,Hara Y,De Waard M,Kanagawa M,Itakura M,Takahashi M,Campbell KP,Mori Ydoi
10.1038/nn1904subject
Has Abstractpub_date
2007-06-01 00:00:00pages
691-701issue
6eissn
1097-6256issn
1546-1726pii
nn1904journal_volume
10pub_type
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