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.
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. - In: CELL DEATH AND DIFFERENTIATION. - ISSN 1476-5403. - 22:9(2015), pp. 1425-1436. [10.1038/cdd.2014.227]
Reduced SNAP-25 increases PSD-95 mobility and impairs spine morphogenesis
G. FossatiPrimo
;R. MoriniSecondo
;I. Corradini;F. Antonucci;M. MatteoliUltimo
2015
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.File | Dimensione | Formato | |
---|---|---|---|
cdd2014227.pdf
accesso riservato
Tipologia:
Publisher's version/PDF
Dimensione
4.81 MB
Formato
Adobe PDF
|
4.81 MB | Adobe PDF | Visualizza/Apri Richiedi una copia |
Reduced SNAP-25 increases PSD-95 mobility and impairs spine morphogenesis.pdf
accesso aperto
Tipologia:
Post-print, accepted manuscript ecc. (versione accettata dall'editore)
Dimensione
495.05 kB
Formato
Adobe PDF
|
495.05 kB | Adobe PDF | Visualizza/Apri |
Pubblicazioni consigliate
I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.