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

Marinka Brouwer, Fatima Farzana, Frank Koopmans, Ning Chen, Jessie W. Brunner, Silvia Oldani, Ka Wan Li, Jan R. T. van Weering, August B. Smit, Ruud F. Toonen, Matthijs Verhage

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13 Citations (Scopus)


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.
Original languageEnglish
Article numbere101289
Pages (from-to)1-20
Number of pages20
JournalEMBO Journal
Issue number17
Early online date1 Aug 2019
Publication statusPublished - 2 Sept 2019


  • Actins/metabolism
  • Animals
  • Calcium-Binding Proteins/metabolism
  • Cell Adhesion Molecules, Neuronal/metabolism
  • Cells, Cultured
  • HEK293 Cells
  • Hippocampus/cytology
  • Humans
  • Membrane Glycoproteins/genetics
  • Mice
  • Nerve Tissue Proteins/genetics
  • Neural Cell Adhesion Molecules/metabolism
  • Neurogenesis
  • PIP2
  • Phosphatidylinositol 4,5-Diphosphate/metabolism
  • SALM1
  • Synapses/metabolism
  • neurexin
  • synapse organization
  • synaptogenesis

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