Orchestration of stepwise synaptic growth by K+ and Ca 2+ channels in Drosophila

Abstract

Synapse formation is tightly associated with neuronal excitability. We found striking synaptic overgrowth caused by Drosophila K+-channel mutations of the seizure and slowpoke genes, encoding Erg and Ca 2+-activated large-conductance (BK) channels, respectively. These mutants display two distinct patterns of "satellite" budding from larval motor terminus synaptic boutons. Double-mutant analysis indicates thatBKand Erg K+ channels interact with separate sets of synaptic proteins to affect distinct growth steps. Post-synaptic L-type Ca2+ channels, Dmca1D, and PSD-95-like scaffold protein, Discs large, are required for satellite budding induced by slowpoke and seizure mutations. Pre-synaptic cacophony Ca2+ channels and the NCAM-like adhesion molecule, Fasciclin II, take part in a maturation step that is partially arrested by seizure mutations. Importantly, slowpoke and seizure satellites were both suppressed by rutabaga mutations that disrupt Ca2+/CaM-dependent adenylyl cyclase, demonstrating a convergence of K+ channels of different functional categories in regulation of excitability-dependent Ca 2+ influx for triggering cAMP-mediated growth plasticity. Copyright © 2010 the authors.