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
