title: Reduced SNAP-25 increases PSD-95 mobility and impairs spine morphogenesis.
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.
authors: 1] Department of Biotechnology and Translational Medicine, University of Milan, Milano 20129, Italy [2] Humanitas Clinical and Research Center, Laboratory of Pharmacology and Brain Pathology, Via Manzoni 56, Rozzano, 20089 Milano, Italy.
authors: G
authors: G
authors: Fossati
authors: 1] Department of Biotechnology and Translational Medicine, University of Milan, Milano 20129, Italy [2] Humanitas Clinical and Research Center, Laboratory of Pharmacology and Brain Pathology, Via Manzoni 56, Rozzano, 20089 Milano, Italy.
authors: R
authors: R
authors: Morini
authors: 1] Department of Biotechnology and Translational Medicine, University of Milan, Milano 20129, Italy [2] Istituto di Neuroscienze del CNR, Milano 20129, Italy.
authors: I
authors: I
authors: Corradini
authors: 1] Department of Biotechnology and Translational Medicine, University of Milan, Milano 20129, Italy [2] Istituto di Neuroscienze del CNR, Milano 20129, Italy.
authors: F
authors: F
authors: Antonucci
authors: Neuroproteomics, Max Delbrueck Center for Molecular Medicine (MDC), Berlin 13125, Germany.
authors: P
authors: P
authors: Trepte
authors: Sagol Department of Neurobiology, Center for Gene Manipulation in the Adult Brain (CGMB), Haifa University, Haifa, Israel.
authors: E
authors: E
authors: Edry
authors: Sagol Department of Neurobiology, Center for Gene Manipulation in the Adult Brain (CGMB), Haifa University, Haifa, Israel.
authors: V
authors: V
authors: Sharma
authors: Division of Neuroscience, Institute of Experimental Neurology, San Raffaele Scientific Institute and University, Milano 20132, Italy.
authors: A
authors: A
authors: Papale
authors: Humanitas Clinical and Research Center, Laboratory of Pharmacology and Brain Pathology, Via Manzoni 56, Rozzano, 20089 Milano, Italy.
authors: D
authors: D
authors: Pozzi
authors: Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino 10124, Italy.
authors: P
authors: P
authors: Defilippi
authors: 1] RNA Editing and Hyperexcitability Disorders Helmholtz Group, Max Delbrück Center for Molecular Medicine, Berlin, Germany [2] TU Braunschweig, Zoological Institute, Division of Cell Biology and Cell Physiology, Braunschweig, Germany.
authors: J C
authors: JC
authors: Meier
authors: Division of Neuroscience, Institute of Experimental Neurology, San Raffaele Scientific Institute and University, Milano 20132, Italy.
authors: R
authors: R
authors: Brambilla
authors: Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino 10124, Italy.
authors: E
authors: E
authors: Turco
authors: Sagol Department of Neurobiology, Center for Gene Manipulation in the Adult Brain (CGMB), Haifa University, Haifa, Israel.
authors: K
authors: K
authors: Rosenblum
authors: Neuroproteomics, Max Delbrueck Center for Molecular Medicine (MDC), Berlin 13125, Germany.
authors: E E
authors: EE
authors: Wanker
authors: Network Biology Labs and Faculty of Medicine, Technion, 33000 Haifa, Israel.
authors: N E
authors: NE
authors: Ziv
authors: 1] Humanitas Clinical and Research Center, Laboratory of Pharmacology and Brain Pathology, Via Manzoni 56, Rozzano, 20089 Milano, Italy [2] Istituto di Neuroscienze del CNR, Milano 20129, Italy.
authors: E
authors: E
authors: Menna
authors: 1] Department of Biotechnology and Translational Medicine, University of Milan, Milano 20129, Italy [2] Humanitas Clinical and Research Center, Laboratory of Pharmacology and Brain Pathology, Via Manzoni 56, Rozzano, 20089 Milano, Italy.
authors: M
authors: M
authors: Matteoli
mesh_terms: D000818:Animals; D049229:Dendritic Spines / Q000378:metabolism / Q000502:physiology*; D000076122:Disks Large Homolog 4 Protein; D051528:Guanylate Kinases / Q000378:metabolism*; D057809:HEK293 Cells; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009024:Morphogenesis; D009473:Neuronal Plasticity / Q000502:physiology; D013569:Synapses / Q000378:metabolism; D050825:Synaptosomal-Associated Protein 25 / Q000378:metabolism*; D014162:Transfection
chemical_list: C501444:DLG4 protein, human; D000076122:Disks Large Homolog 4 Protein; C501447:Dlg4 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C494208:SNAP25 protein, human; C494209:Snap25 protein, mouse; D050825:Synaptosomal-Associated Protein 25; D051528:Guanylate Kinases