SALM1 controls synapse development by promoting F-actin/PIP2-dependent Neurexin clustering

Marinka Brouwer; Fatima Farzana; Frank Koopmans; Ning Chen; Jessie W. Brunner; Silvia Oldani; Ka Wan Li; Jan R. T. van Weering; August B. Smit; Ruud F. Toonen; Matthijs Verhage

doi:10.15252/embj.2018101289

SALM1 controls synapse development by promoting F-actin/PIP2-dependent Neurexin clustering

Marinka Brouwer, Fatima Farzana, Frank Koopmans, Ning Chen, Jessie W. Brunner, Silvia Oldani, Ka Wan Li, Jan R. T. van Weering, August B. Smit, Ruud F. Toonen, Matthijs Verhage

Research output: Contribution to journal › Article › Academic › peer-review

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 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.

Original language	English
Article number	e101289
Journal	EMBO Journal
Volume	38
Issue number	17
DOIs	https://doi.org/10.15252/embj.2018101289
Publication status	Published - 2 Sep 2019

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title = "SALM1 controls synapse development by promoting F-actin/PIP2-dependent Neurexin clustering",

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 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.",

keywords = "PIP2, SALM1, neurexin, synapse organization, synaptogenesis",

author = "Marinka Brouwer and Fatima Farzana and Frank Koopmans and Ning Chen and Brunner, {Jessie W.} and Silvia Oldani and Li, {Ka Wan} and {van Weering}, {Jan R. T.} and Smit, {August B.} and Toonen, {Ruud F.} and Matthijs Verhage",

year = "2019",

month = sep,

day = "2",

doi = "10.15252/embj.2018101289",

language = "English",

volume = "38",

journal = "EMBO Journal",

issn = "0261-4189",

publisher = "Wiley-Blackwell",

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T1 - SALM1 controls synapse development by promoting F-actin/PIP2-dependent Neurexin clustering

AU - Brouwer, Marinka

AU - Farzana, Fatima

AU - Koopmans, Frank

AU - Chen, Ning

AU - Brunner, Jessie W.

AU - Oldani, Silvia

AU - Li, Ka Wan

AU - van Weering, Jan R. T.

AU - Smit, August B.

AU - Toonen, Ruud F.

AU - Verhage, Matthijs

PY - 2019/9/2

Y1 - 2019/9/2

N2 - 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.

AB - 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.

KW - PIP2

KW - SALM1

KW - neurexin

KW - synapse organization

KW - synaptogenesis

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U2 - 10.15252/embj.2018101289

DO - 10.15252/embj.2018101289

M3 - Article

C2 - 31368584

VL - 38

JO - EMBO Journal

JF - EMBO Journal

SN - 0261-4189

IS - 17

M1 - e101289

ER -

SALM1 controls synapse development by promoting F-actin/PIP2-dependent Neurexin clustering

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