New study on synapse development published in EMBO J

August 13, 2019


In this study Marinka Brouwer (FGA) shows that adhesion molecule SALM1 binds an intracellular protein complex via one domain and organizes synapse development via another. The study was a collaboration between FGA and MCN.

Synapse development requires spatiotemporally regulated recruitment of synaptic proteins. In this study, Marinka Brouwer and her team describe a novel presynaptic mechanism of cis-regulated oligomerization of adhesion molecules that controls synaptogenesis. The study identifies 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.

The paper is published on August 1st in the EMBO Journal and is available here