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PMID: 18439405 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

A presynaptic giant ankyrin stabilizes the NMJ through regulation of presynaptic microtubules and transsynaptic cell adhesion.

Neuron ·Vol. 58 ·No. 2 ·2008-04-24 ·Pages 195-209

Pielage J, Cheng L, Fetter RD, Carlton PM, Sedat JW, Davis GW

Abstract

In a forward genetic screen for mutations that destabilize the neuromuscular junction, we identified a novel long isoform of Drosophila ankyrin2 (ank2-L). We demonstrate that loss of presynaptic Ank2-L not only causes synapse disassembly and retraction but also disrupts neuronal excitability and NMJ morphology. We provide genetic evidence that ank2-L is necessary to generate the membrane constrictions that normally separate individual synaptic boutons and is necessary to achieve the normal spacing of subsynaptic protein domains, including the normal organization of synaptic cell adhesion molecules. Mechanistically, synapse organization is correlated with a lattice-like organization of Ank2-L, visualized using extended high-resolution structured-illumination microscopy. The stabilizing functions of Ank2-L can be mapped to the extended C-terminal domain that we demonstrate can directly bind and organize synaptic microtubules. We propose that a presynaptic Ank2-L lattice links synaptic membrane proteins and spectrin to the underlying microtubule cytoskeleton to organize and stabilize the presynaptic terminal.

MeSH Terms
Amino Acid Motifs/physiology Animals Animals, Genetically Modified Ankyrins/genetics Cell Adhesion Molecules, Neuronal/metabolism Drosophila Drosophila Proteins/genetics Gene Expression Regulation/genetics Horseradish Peroxidase/metabolism Larva Luminescent Proteins/genetics,metabolism Microscopy, Electron, Transmission/methods Microtubules/metabolism Mutation/genetics Neuromuscular Junction/physiology,ultrastructure Presynaptic Terminals/metabolism,ultrastructure Synapsins/metabolism Synaptic Transmission/genetics
Chemicals
Ank2 protein, Drosophila Ankyrins Cell Adhesion Molecules, Neuronal Drosophila Proteins Luminescent Proteins Synapsins fasciclin II Horseradish Peroxidase
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Pielage Jan
Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158-2822, USA.
Cheng Ling
Fetter Richard D
Carlton Pete M
Sedat John W
Davis Graeme W
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Article Info
Journal
Neuron
Abbr.
Neuron
ISSN
1097-4199
DOI
10.1016/j.neuron.2008.02.017
Published
2008-04-24
Pages
195-209
Language
English
Region
United States
NLM ID
8809320
PMCID
PMC2699047
Subset
IM
Grants
NINDS NIH HHS · R01 NS059867-04 · United States
NINDS NIH HHS · R37 NS047342 · United States
NINDS NIH HHS · R01 NS047342 · United States
NINDS NIH HHS · R01 NS059867 · United States
NINDS NIH HHS · NS047342 · United States
NINDS NIH HHS · R01 NS047342-05 · United States
External Links
PubMed source DOI: 10.1016/j.neuron.2008.02.017 PMC Full Text View journal details
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