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

Fossati, G., Morini, R., Corradini, I., Antonucci, F., Trepte, P., Edry, E., Sharma, V., Papale, Alessandro, Pozzi, D., Defilippi, P., Meier, J. C., Brambilla, Riccardo, Turco, E., Rosenblum, K., Wanker, E. E., Ziv, N. E., Menna, E. and Matteoli, M. 2015. Reduced SNAP-25 increases PSD-95 mobility and impairs spine morphogenesis. Cell Death and Differentiation 22 , pp. 1425-1436. 10.1038/cdd.2014.227

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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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Additional Information: Advance online publication 13 February 2015 PDF uploaded in accordance with publisher's policies at (accessed 13/11/15).
Publisher: Nature Publishing Group
ISSN: 1350-9047
Date of First Compliant Deposit: 30 March 2016
Date of Acceptance: 26 November 2014
Last Modified: 04 Jun 2017 08:21

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