Mutation of Drosophila Focal Adhesion Kinase Induces Bang-Sensitive Behavior and Disrupts Glial Function, Axonal Conduction and Synaptic Transmission

Atsushi Ueda; Caroline Grabbe; Jihye Lee; Jisue Lee; Ruth H Palmer; Chun-Fang Wu

doi:10.1111/j.1460-9568.2008.06252.x

Back

Mutation of Drosophila Focal Adhesion Kinase Induces Bang-Sensitive Behavior and Disrupts Glial Function, Axonal Conduction and Synaptic Transmission

Journal article

Peer reviewed

Mutation of Drosophila Focal Adhesion Kinase Induces Bang-Sensitive Behavior and Disrupts Glial Function, Axonal Conduction and Synaptic Transmission

Atsushi Ueda, Caroline Grabbe, Jihye Lee, Jisue Lee, Ruth H Palmer and Chun-Fang Wu

The European journal of neuroscience, Vol.27(11), pp.2860-2870

06/2008

DOI: 10.1111/j.1460-9568.2008.06252.x

PMCID: PMC2671471

PMID: 18540882

Files and links (1)

url

http://doi.org/10.1111/j.1460-9568.2008.06252.xView

Open Access

Abstract

The role of the conserved Focal Adhesion Kinase (FAK) family of protein tyrosine kinases (PTKs) in the development and physiological functions of the CNS has long been an area of interest among neuroscientists. In this report, we observe that Drosophila mutants lacking Fak56 exhibit a decreased life span, accompanied by a bang-sensitive phenotype, which is characterised by sensitivity to mechanical and high-frequency electrical stimulation. Fak56 mutant animals display lower thresholds and higher rates of seizures in response to electroconvulsive stimuli, and direct measurements of action potential conduction in larval segmental nerves demonstrate a slowed propagation speed and failure during high-frequency nerve stimulation. In addition, neuromuscular junctions in Fak56 mutant animals display transmission blockade during high-frequency activity as a result of action potential failure. Endogenous Fak56 protein is abundant in glial cells ensheathing the axon bundles, and structural alterations of segmental nerve bundles can be observed in mutants. Manipulation of Fak56 function specifically in glial cells also disrupts action potential conduction and neurotransmission, suggesting a glial component in the Fak56 bang-sensitive phenotype. Furthermore, we show that increased intracellular calcium levels result in the dephosphorylation of endogenous Fak56 protein in Drosophila cell lines, in parallel with our observations of highly variable synaptic potentials at a higher Ca 2+ level in Fak56 mutant larvae. Together these findings suggest that modulation of Fak56 function is important for action potential propagation and Ca 2+ -regulated neuromuscular transmission in vivo .

Fak56

calcium

tyrosine phosphorylation

neuromuscular junction

glia

Details

Title: Subtitle: Mutation of Drosophila Focal Adhesion Kinase Induces Bang-Sensitive Behavior and Disrupts Glial Function, Axonal Conduction and Synaptic Transmission
Creators: Atsushi Ueda - Department of Biological Sciences, University of Iowa, Iowa City, Iowa 52242, USA
Caroline Grabbe - Umeå Center for Molecular Pathogenesis, Building 6L, Umeå University, Umeå, S-901 87, Sweden
Jihye Lee - Interdisciplinary Program in Neuroscience, University of Iowa, Iowa City, Iowa 52242, USA
Jisue Lee - Department of Biological Sciences, University of Iowa, Iowa City, Iowa 52242, USA
Ruth H Palmer - Umeå Center for Molecular Pathogenesis, Building 6L, Umeå University, Umeå, S-901 87, Sweden
Chun-Fang Wu - Department of Biological Sciences, University of Iowa, Iowa City, Iowa 52242, USA
Resource Type: Journal article
Publication Details: The European journal of neuroscience, Vol.27(11), pp.2860-2870
DOI: 10.1111/j.1460-9568.2008.06252.x
PMID: 18540882
PMCID: PMC2671471
NLM abbreviation: Eur J Neurosci
ISSN: 0953-816X
eISSN: 1460-9568
Language: English
Date published: 06/2008
Academic Unit: Iowa Neuroscience Institute; Biology
Record Identifier: 9984070450202771

Metrics

27 Record Views

20 Times Cited - Web of Science