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 Rt van Weering, August B Smit, Ruud F Toonen, Matthijs Verhage

The EMBO journal 2019 Sep 02

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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. © 2019 The Authors. Published under the terms of the CC BY 4.0 license.

Citation

Marinka Brouwer, Fatima Farzana, Frank Koopmans, Ning Chen, Jessie W Brunner, Silvia Oldani, Ka Wan Li, Jan Rt van Weering, August B Smit, Ruud F Toonen, Matthijs Verhage. SALM1 controls synapse development by promoting F-actin/PIP2-dependent Neurexin clustering. The EMBO journal. 2019 Sep 02;38(17):e101289