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Published 6 November 2006. doi:10.1083/jcb.200607036
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 175, Number 3, 491-503
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Article

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



Jan Pielage1,2, Richard D. Fetter1,2, and Graeme W. Davis1,2

1 Department of Biochemistry and Biophysics and 2 Program in Neuroscience, University of California, San Francisco, San Francisco, CA 94143

Correspondence to Graeme W. Davis: gdavis{at}biochem.ucsf.edu

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, ß-Spectrin, or Ankyrin. In the absence of postsynaptic {alpha}- or ß-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, ß-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.

Abbreviations used in this paper: ds, double stranded; EPSP, excitatory postsynaptic potential; mepsp, miniature EPSP; NMJ, neuromuscular junction; Pak, p21-activated kinase; RNAi, RNA interference; SSR, subsynaptic recombination.


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