SALM1 controls synapse development by promoting F‐actin/PIP2‐dependent Neurexin clustering

• Marinka Brouwer ^[1] ; Fatima Farzana ^[2] ; Frank Koopmans ^[3] ; Ning Chen ^[3] ; Jessie W Brunner ^[2] ; Silvia Oldani ^[2] ; Ka Wan Li ^[4] ; Jan RT van Weering ^[1] ; August B Smit ^[4] ; Ruud F Toonen ^[2] ; Matthijs Verhage ^[5]
  1. [1] 1 Department of Clinical Genetics Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience VU University Amsterdam and VU Medical Center Amsterdam The Netherlands
  2. [2] 2 Department of Functional Genomics Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience VU University Amsterdam and VU Medical Center Amsterdam The Netherlands
  3. [3] 2 Department of Functional Genomics Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience VU University Amsterdam and VU Medical Center Amsterdam The Netherlands; 3 Department of Molecular and Cellular Neurobiology Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience VU University Amsterdam and VU Medical Center Amsterdam The Netherlands
  4. [4] 3 Department of Molecular and Cellular Neurobiology Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience VU University Amsterdam and VU Medical Center Amsterdam The Netherlands
  5. [5] 1 Department of Clinical Genetics Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience VU University Amsterdam and VU Medical Center Amsterdam The Netherlands; 2 Department of Functional Genomics Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience VU University Amsterdam and VU Medical Center Amsterdam The Netherlands

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• Localización: EMBO journal: European Molecular Biology Organization, ISSN 0261-4189, Vol. 38, Nº. 17, 2019
• Idioma: inglés
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  • Synapse development requires spatiotemporally regulated recruitment of synaptic proteins. In this study, we describe a novel presynaptic mechanism of cis‐regulated oligomerization of adhesion molecules that controls synaptogenesis. We identified synaptic adhesion‐like molecule 1 (SALM1) as a constituent of the proposed presynaptic Munc18/CASK/Mint1/Lin7b organizer complex. SALM1 preferentially localized to presynaptic compartments of excitatory hippocampal neurons. SALM1 depletion in excitatory hippocampal primary neurons impaired Neurexin1β‐ and Neuroligin1‐mediated excitatory synaptogenesis and reduced synaptic vesicle clustering, synaptic transmission, and synaptic vesicle release. SALM1 promoted Neurexin1β clustering in an F‐actin‐ and PIP2‐dependent manner. Two basic residues in SALM1's juxtamembrane polybasic domain are essential for this clustering. Together, these data show that SALM1 is a presynaptic organizer of synapse development by promoting F‐actin/PIP2‐dependent clustering of Neurexin.