A presynaptic homeostatic signaling system composed of the Eph receptor, ephexin, Cdc42, and CaV2.1 calcium channels

C Andrew Frank; Jan Pielage; Graeme W Davis

doi:10.1016/j.neuron.2008.12.028

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A presynaptic homeostatic signaling system composed of the Eph receptor, ephexin, Cdc42, and CaV2.1 calcium channels

Journal article

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A presynaptic homeostatic signaling system composed of the Eph receptor, ephexin, Cdc42, and CaV2.1 calcium channels

C Andrew Frank, Jan Pielage and Graeme W Davis

Neuron (Cambridge, Mass.), Vol.61(4), pp.556-569

02/26/2009

DOI: 10.1016/j.neuron.2008.12.028

PMCID: PMC2699049

PMID: 19249276

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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.

Immunohistochemistry

Guanine Nucleotide Exchange Factors - physiology

Synaptic Transmission - physiology

Receptors, Presynaptic - physiology

Electrophysiology

Molecular Sequence Data

Drosophila - physiology

Receptors, Presynaptic - genetics

Mutation - physiology

Drosophila Proteins - physiology

Amino Acid Sequence

Calcium Channels, N-Type - genetics

Guanine Nucleotide Exchange Factors - genetics

Muscles - physiology

Neurotransmitter Agents - metabolism

Signal Transduction - genetics

cdc42 GTP-Binding Protein - physiology

Mutation - genetics

Receptor, EphA1 - physiology

Animals

cdc42 GTP-Binding Protein - genetics

Homeostasis - physiology

Receptor, EphA1 - genetics

Calcium Channels, N-Type - physiology

Muscles - innervation

Signal Transduction - physiology

Drosophila Proteins - genetics

Homeostasis - genetics

Receptors, Glutamate - physiology

Details

Title: Subtitle: A presynaptic homeostatic signaling system composed of the Eph receptor, ephexin, Cdc42, and CaV2.1 calcium channels
Creators: C Andrew Frank - Department of Biochemistry and Biophysics, 1550 4th Street, Rock Hall 4th Floor North, University of California, San Francisco, San Francisco, CA 94158, USA
Jan Pielage
Graeme W Davis
Resource Type: Journal article
Publication Details: Neuron (Cambridge, Mass.), Vol.61(4), pp.556-569
Publisher: United States
DOI: 10.1016/j.neuron.2008.12.028
PMID: 19249276
PMCID: PMC2699049
ISSN: 0896-6273
eISSN: 1097-4199
Grant note: NS39313 / NINDS NIH HHS F32 NS049694-02 / NINDS NIH HHS R01 NS039313 / NINDS NIH HHS K99 NS062738-01 / NINDS NIH HHS R00 NS062738 / NINDS NIH HHS F32 NS049694-03 / NINDS NIH HHS R01 NS039313-09 / NINDS NIH HHS K99 NS062738 / NINDS NIH HHS F32 NS049694-01 / NINDS NIH HHS NS062738 / NINDS NIH HHS F32 NS049694 / NINDS NIH HHS NS049694 / NINDS NIH HHS
Language: English
Date published: 02/26/2009
Academic Unit: Anatomy and Cell Biology; Iowa Neuroscience Institute
Record Identifier: 9984025449702771

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