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 journalArticlepeer-review

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
StatePublished - 11 Sep 2015

Bibliographical note

Funding Information:
Acknowledgements. We wish to acknowledge Professor Reinhard Jahn (MPI, Goettingen) for his valuable suggestions. Dr Simona Rodighiero (Fondazione Filarete, Milano, Italy) for assistance with FRAP experiments, Dr Cristina Sobacchi (Istituto Clinico Humanitas, Rozzano, Italy) for helping with C57BL/6J-GFP colony and Martina Zenkner (MDC, Berlin, Germany) for technical assistance. We would like to thank the Monzino Foundation (Milano, Italy) for its generous gift of the LSM 510 Meta and Perkin Elmer Ultraview confocal microscopes. The research leading to these results has received funding from the European Union Seventh Framework Programme under grant agreement n° HEALTH-F2-2009-241498 (‘EUROSPIN’ project) to MM, NEZ, KR, and EW; BMBF, ERA-Net Neuron II CIPRESS to JCM; by the Italian Ministry of Health (RF-2009-1545998 to MM and RF-2009-1471694 to RB) and by PRIN 2011 and Cariplo 2011-0540 to MM, and by CNR Research Project on Aging, Regione Lombardia Project MbMM-convenzione n°18099/RCC.

Publisher Copyright:
© 2015 Macmillan Publishers Limited.

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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