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

Item Type:Article
Title:Reduced SNAP-25 increases PSD-95 mobility and impairs spine morphogenesis
Creators Name:Fossati, G. and Morini, R. and Corradini, I. and Antonucci, F. and Trepte, P. and Edry, E. and Sharma, V. and Papale, A. and Pozzi, D. and Defilippi, P. and Meier, J.C. and Brambilla, R. and Turco, E. and Rosenblum, K. and Wanker, E.E. and Ziv, N.E. and 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
Publisher:Nature Publishing Group
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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