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The Journal of Neuroscience, January 31, 2007, 27(5):1033-1044; doi:10.1523/JNEUROSCI.3160-06.2007

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Cellular/Molecular
Postsynaptic Membrane Addition Depends on the Discs-Large-Interacting t-SNARE Gtaxin

David Gorczyca,1 * James Ashley,1 * Sean Speese,1 Norberto Gherbesi,1 Ulrich Thomas,2 Eckart Gundelfinger,2 L. Sian Gramates,3 and Vivian Budnik1

1Department of Neurobiology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, 2Leibniz Institute for Neurobiology, 39118 Magdeburg, Germany, and 3Molecular and Cellular Biology Graduate Program, University of Massachusetts at Amherst, Amherst, Massachusetts 01003

Correspondence should be addressed to Vivian Budnik, Department of Neurobiology, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605. Email: Vivian.Budnik{at}umassmed.edu

Targeted membrane addition is a hallmark of many cellular functions. In the nervous system, modification of synaptic membrane size has a major impact on synaptic function. However, because of the complex shape of neurons and the need to target membrane addition to very small and polarized synaptic compartments, this process is poorly understood. Here, we show that Gtaxin (GTX), a Drosophila t-SNARE (target-soluble N-ethylmaleimide-sensitive factor attachment protein receptor), is required for expansion of postsynaptic membranes during new synapse formation. Mutations in gtx lead to drastic reductions in postsynaptic membrane surface, whereas gtx upregulation results in the formation of complex membrane structures at ectopic sites. Postsynaptic GTX activity depends on its direct interaction with Discs-Large (DLG), a multidomain scaffolding protein of the PSD-95 (postsynaptic density protein-95) family with key roles in cell polarity and formation of cellular junctions as well as synaptic protein anchoring and trafficking. We show that DLG selectively determines the postsynaptic distribution of GTX to type I, but not to type II or type III boutons on the same cell, thereby defining sites of membrane addition to this unique set of glutamatergic synapses. We provide a mechanistic explanation for selective targeted membrane expansion at specific synaptic junctions.

Key words: postsynaptic plasticity; neuromuscular junction; Discs-large; Drosophila; membrane addition; MAGUK


Received July 24, 2006; revised Nov. 20, 2006; accepted Dec. 20, 2006.

Correspondence should be addressed to Vivian Budnik, Department of Neurobiology, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605. Email: Vivian.Budnik{at}umassmed.edu


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