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
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.
|Institution:||The University of York|
|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|
|Publisher:||Elsevier (Cell Press)|