SALM1 controls synapse development by promoting F-actin/PIP2-dependent Neurexin clustering
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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.
Brouwer, M., Farzana, F., Koopmans, F., Chen, N., Brunner, J. W., Oldani, S., ... Verhage, M. (2019). SALM1 controls synapse development by promoting F-actin/PIP2-dependent Neurexin clustering. EMBO Journal, 38(17), [e101289]. https://doi.org/10.15252/embj.2018101289