| First Author | Brouwer M | Year | 2019 |
| Journal | EMBO J | Volume | 38 |
| Issue | 17 | Pages | e101289 |
| PubMed ID | 31368584 | Mgi Jnum | J:326510 |
| Mgi Id | MGI:6454751 | Doi | 10.15252/embj.2018101289 |
| Citation | Brouwer M, et al. (2019) SALM1 controls synapse development by promoting F-actin/PIP2-dependent Neurexin clustering. EMBO J 38(17):e101289 |
| abstractText | 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 Neurexin1beta- and Neuroligin1-mediated excitatory synaptogenesis and reduced synaptic vesicle clustering, synaptic transmission, and synaptic vesicle release. SALM1 promoted Neurexin1beta 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. |
