SALM1 controls synapse development by promoting F-actin/PIP2-dependent Neurexin clustering.
EMBO J
; 38(17): e101289, 2019 09 02.
Article
em En
| MEDLINE
| ID: mdl-31368584
ABSTRACT
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 Neurexin1ß- and Neuroligin1-mediated excitatory synaptogenesis and reduced synaptic vesicle clustering, synaptic transmission, and synaptic vesicle release. SALM1 promoted Neurexin1ß 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.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Sinapses
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Proteínas de Ligação ao Cálcio
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Glicoproteínas de Membrana
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Actinas
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Moléculas de Adesão de Célula Nervosa
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Fosfatidilinositol 4,5-Difosfato
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Proteínas do Tecido Nervoso
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article