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Unrestricted synaptic growth in spinster - A late endosomal protein implicated in TGF-ß-mediated synaptic growth regulation

Sweeney, S.T. and Davis, G.W. (2002) Unrestricted synaptic growth in spinster - A late endosomal protein implicated in TGF-ß-mediated synaptic growth regulation. Neuron, 36 (3). pp. 403-416. ISSN 0896-6273

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Abstract

In a genetic screen for genes that control synapse development, we have identified spinster (spin), which encodes a multipass transmembrane protein. spin mutant synapses reveal a 200% increase in bouton number and a deficit in presynaptic release. We demonstrate that spin is expressed in both nerve and muscle and is required both pre- and postsynaptically for normal synaptic growth. We have localized Spin to a late endosomal compartment and present evidence for altered endosomal/lysosomal function in spin. We also present evidence that synaptic overgrowth in spin is caused by enhanced/misregulated TGF-β signaling. TGF-β receptor mutants show dose-dependent suppression of synaptic overgrowth in spin. Furthermore, mutations in Dad, an inhibitory Smad, cause synapse overgrowth. We present a model for synaptic growth control with implications for the etiology of lysosomal storage and neurodegenerative disease.

Item Type: Article
Academic Units: The University of York > Biology (York)
Depositing User: York RAE Import
Date Deposited: 09 Feb 2009 11:52
Last Modified: 09 Feb 2009 11:52
Published Version: http://dx.doi.org/10.1016/S0896-6273(02)01014-0
Status: Published
Publisher: Elsevier (Cell Press)
Identification Number: 10.1016/S0896-6273(02)01014-0
URI: http://eprints.whiterose.ac.uk/id/eprint/7675

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