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
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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Dates: |
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Institution: | The University of York |
Academic Units: | The University of York > Faculty of Sciences (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 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:7675 |