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 ORCID: https://orcid.org/0000-0002-8794-0171, Pozzi, D., Defilippi, P., Meier, J. C., Brambilla, Riccardo ORCID: https://orcid.org/0000-0003-3569-5706, 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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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.

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 http://www.sherpa.ac.uk/romeo/issn/1350-9047/ (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:	05 May 2023 18:27
URI:	https://orca.cardiff.ac.uk/id/eprint/76271

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