SALM1 controls synapse development by promoting F-actin/PIP2-dependent Neurexin clustering.
Actins
/ metabolism
Animals
Calcium-Binding Proteins
/ metabolism
Cell Adhesion Molecules, Neuronal
/ metabolism
Cells, Cultured
HEK293 Cells
Hippocampus
/ cytology
Humans
Membrane Glycoproteins
/ genetics
Mice
Nerve Tissue Proteins
/ genetics
Neural Cell Adhesion Molecules
/ metabolism
Neurogenesis
Phosphatidylinositol 4,5-Diphosphate
/ metabolism
Synapses
/ metabolism
PIP2
SALM1
neurexin
synapse organization
synaptogenesis
Journal
The EMBO journal
ISSN: 1460-2075
Titre abrégé: EMBO J
Pays: England
ID NLM: 8208664
Informations de publication
Date de publication:
02 09 2019
02 09 2019
Historique:
received:
03
12
2018
revised:
20
06
2019
accepted:
25
06
2019
pubmed:
2
8
2019
medline:
24
12
2019
entrez:
2
8
2019
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 31368584
doi: 10.15252/embj.2018101289
pmc: PMC6717895
doi:
Substances chimiques
Actins
0
Calcium-Binding Proteins
0
Cell Adhesion Molecules, Neuronal
0
Lrfn2 protein, mouse
0
Membrane Glycoproteins
0
Nerve Tissue Proteins
0
Neural Cell Adhesion Molecules
0
Nrxn1 protein, mouse
0
Phosphatidylinositol 4,5-Diphosphate
0
neuroligin 1
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e101289Subventions
Organisme : European Research Council
ID : 322966
Pays : International
Organisme : ZonMw (Netherlands Organisation for Health Research and Development)
ID : 91111009
Pays : International
Informations de copyright
© 2019 The Authors. Published under the terms of the CC BY 4.0 license.
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