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SALM 1 controls synapse development by promoting F‐actin/PIP2‐dependent Neurexin clustering
Author(s) -
Brouwer Marinka,
Farzana Fatima,
Koopmans Frank,
Chen Ning,
Brunner Jessie W,
Oldani Silvia,
Li Ka Wan,
van Weering Jan RT,
Smit August B,
Toonen Ruud F,
Verhage Matthijs
Publication year - 2019
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.2018101289
Subject(s) - neuroscience , research center , center (category theory) , library science , psychology , computer science , medicine , chemistry , pathology , crystallography
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 ( SALM 1) as a constituent of the proposed presynaptic Munc18/ CASK /Mint1/Lin7b organizer complex. SALM 1 preferentially localized to presynaptic compartments of excitatory hippocampal neurons. SALM 1 depletion in excitatory hippocampal primary neurons impaired Neurexin1β‐ and Neuroligin1‐mediated excitatory synaptogenesis and reduced synaptic vesicle clustering, synaptic transmission, and synaptic vesicle release. SALM 1 promoted Neurexin1β clustering in an F‐actin‐ and PIP 2‐dependent manner. Two basic residues in SALM 1's juxtamembrane polybasic domain are essential for this clustering. Together, these data show that SALM 1 is a presynaptic organizer of synapse development by promoting F‐actin/ PIP 2‐dependent clustering of Neurexin.