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

G. Fossati, R. Morini, I. Corradini, F. Antonucci, P. Trepte, E. Edry, V. Sharma, A. Papale, D. Pozzi, P. Defilippi, J. C. Meier, R. Brambilla, E. Turco, K. Rosenblum, E. E. Wanker, N. E. Ziv, E. Menna, M. Matteoli

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)1425-1436
Number of pages12
JournalCell Death and Differentiation
Volume22
Issue number9
DOIs
Publication statusPublished - Sep 11 2015

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

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    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., & Matteoli, M. (2015). Reduced SNAP-25 increases PSD-95 mobility and impairs spine morphogenesis. Cell Death and Differentiation, 22(9), 1425-1436. https://doi.org/10.1038/cdd.2014.227