Frank, C Andrew, Pielage, Jan and Davis, Graeme W (2009) A presynaptic homeostatic signaling system composed of the Eph receptor, ephexin, Cdc42, and CaV2.1 calcium channels. Neuron, 61 (4). pp. 556-569. ISSN 1097-4199

Abstract

The molecular mechanisms underlying the homeostatic modulation of presynaptic neurotransmitter release remain largely unknown. In a screen, we isolated mutations in Drosophila ephexin (Rho-type guanine nucleotide exchange factor) that disrupt the homeostatic enhancement of presynaptic release following impairment of postsynaptic glutamate receptor function at the Drosophila neuromuscular junction. We show that Ephexin is sufficient presynaptically for synaptic homeostasis and localizes in puncta throughout the nerve terminal. However, ephexin mutations do not alter other aspects of neuromuscular development, including morphology or active zone number. We then show that, during synaptic homeostasis, Ephexin functions primarily with Cdc42 in a signaling system that converges upon the presynaptic CaV2.1 calcium channel. Finally, we show that Ephexin binds the Drosophila Eph receptor (Eph) and Eph mutants disrupt synaptic homeostasis. Based on these data, we propose that Ephexin/Cdc42 couples synaptic Eph signaling to the modulation of presynaptic CaV2.1 channels during the homeostatic enhancement of presynaptic release.

Item Type:	Article
Related URLs:	http://www.ncbi.nlm.nih.gov/sites/entrez...
Additional Information:	author can archive post-print (ie final draft post-refereeing); Publisher's version/PDF cannot be used
Keywords:	MOLNEURO; CELLBIO; SIGNALING
Related URLs:	http://www.ncbi.nlm.nih.gov/sites/entrez...
Date Deposited:	14 Dec 2009 13:50
Last Modified:	14 Dec 2009 13:50
URI:	https://oak.novartis.com/id/eprint/963