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PMID: 17088429 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

A postsynaptic spectrin scaffold defines active zone size, spacing, and efficacy at the Drosophila neuromuscular junction.

The Journal of cell biology ·Vol. 175 ·No. 3 ·2006-11-06 ·Pages 491-503

Pielage J, Fetter RD, Davis GW

Abstract

Synaptic connections are established with characteristic, cell type-specific size and spacing. In this study, we document a role for the postsynaptic Spectrin skeleton in this process. We use transgenic double-stranded RNA to selectively eliminate alpha-Spectrin, beta-Spectrin, or Ankyrin. In the absence of postsynaptic alpha- or beta-Spectrin, active zone size is increased and spacing is perturbed. In addition, subsynaptic muscle membranes are significantly altered. However, despite these changes, the subdivision of the synapse into active zone and periactive zone domains remains intact, both pre- and postsynaptically. Functionally, altered active zone dimensions correlate with an increase in quantal size without a change in presynaptic vesicle size. Mechanistically, beta-Spectrin is required for the localization of alpha-Spectrin and Ankyrin to the postsynaptic membrane. Although Ankyrin is not required for the localization of the Spectrin skeleton to the neuromuscular junction, it contributes to Spectrin-mediated synapse development. We propose a model in which a postsynaptic Spectrin-actin lattice acts as an organizing scaffold upon which pre- and postsynaptic development are arranged.

MeSH Terms
Actins/metabolism Animals Ankyrins/genetics,metabolism Drosophila Proteins/genetics,metabolism Drosophila melanogaster/cytology,growth & development,metabolism Electrophysiology Excitatory Postsynaptic Potentials Larva Microscopy, Electron Muscles/innervation,metabolism Neuromuscular Junction/growth & development,metabolism,ultrastructure Presynaptic Terminals/ultrastructure Protein Transport RNA Interference Spectrin/genetics,metabolism Synaptic Membranes/metabolism
Chemicals
Actins Ankyrins Drosophila Proteins Spectrin
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Pielage Jan
Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94143, USA.
Fetter Richard D
Davis Graeme W
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.200607036
Published
2006-11-06
Pages
491-503
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2064525
Subset
IM
Grants
NINDS NIH HHS · R01 NS047342 · United States
NINDS NIH HHS · R37 NS047342 · United States
NINDS NIH HHS · NS047342 · United States
External Links
PubMed source DOI: 10.1083/jcb.200607036 PMC Full Text View journal details
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