Reduced SNAP-25 increases PSD-95 mobility and impairs spine morphogenesis

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Item Type:	Article
Title:	Reduced SNAP-25 increases PSD-95 mobility and impairs spine morphogenesis
Creators Name:	Fossati, G., Morini, R., Corradini, I., Antonucci, F., Trepte, P., Edry, E., Sharma, V., Papale, A., Pozzi, D., Defilippi, P., Meier, J.C., Brambilla, R., Turco, E., Rosenblum, K., Wanker, E.E., Ziv, N.E., Menna, E. and Matteoli, M.
Abstract:	Impairment of synaptic function can lead to neuropsychiatric disorders collectively referred to as synaptopathies. The SNARE protein SNAP-25 is implicated in several brain pathologies and, indeed, brain areas of psychiatric patients often display reduced SNAP-25 expression. It has been recently found that acute downregulation of SNAP-25 in brain slices impairs long-term potentiation; however, the processes through which this occurs are still poorly defined. We show that in vivo acute downregulation of SNAP-25 in CA1 hippocampal region affects spine number. Consistently, hippocampal neurons from SNAP-25 heterozygous mice show reduced densities of dendritic spines and defective PSD-95 dynamics. Finally, we show that, in brain, SNAP-25 is part of a molecular complex including PSD-95 and p140Cap, with p140Cap being capable to bind to both SNAP-25 and PSD-95. These data demonstrate an unexpected role of SNAP-25 in controlling PSD-95 clustering and open the possibility that genetic reductions of the protein levels - as occurring in schizophrenia - may contribute to the pathology through an effect on postsynaptic function and plasticity.
Keywords:	Dendritic Spines, Guanylate Kinase, HEK293 Cells, Hippocampus, Inbred C57BL Mice, Intracellular Signaling Peptides and Proteins, Membrane Proteins, Morphogenesis, Neuronal Plasticity, Synapses, Synaptosomal-Associated Protein 25, Transfection, Transgenic Mice, Animals, Mice
Source:	Cell Death and Differentiation
ISSN:	1350-9047
Publisher:	Nature Publishing Group
Volume:	22
Number:	9
Page Range:	1425-1436
Date:	September 2015
Additional Information:	Copyright © 2015, Macmillan Publishers Limited
Official Publication:	https://doi.org/10.1038/cdd.2014.227
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PubMed:	View item in PubMed

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