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:https://doi.org/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

13 Citations (Scopus)

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
Pages (from-to)	1-20
Number of pages	20
Journal	EMBO Journal
Volume	38
Issue number	17
Early online date	1 Aug 2019
DOIs	https://doi.org/10.15252/embj.2018101289
Publication status	Published - 2 Sept 2019

Keywords

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
PIP2
Phosphatidylinositol 4,5-Diphosphate/metabolism
SALM1
Synapses/metabolism
neurexin
synapse organization
synaptogenesis

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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https://doi.org/10.15252/embj.2018101289

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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.",

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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",

note = "{\textcopyright} 2019 The Authors. Published under the terms of the CC BY 4.0 license.",

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doi = "https://doi.org/10.15252/embj.2018101289",

language = "English",

volume = "38",

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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 - Actins/metabolism

KW - Animals

KW - Calcium-Binding Proteins/metabolism

KW - Cell Adhesion Molecules, Neuronal/metabolism

KW - Cells, Cultured

KW - HEK293 Cells

KW - Hippocampus/cytology

KW - Humans

KW - Membrane Glycoproteins/genetics

KW - Mice

KW - Nerve Tissue Proteins/genetics

KW - Neural Cell Adhesion Molecules/metabolism

KW - Neurogenesis

KW - PIP2

KW - Phosphatidylinositol 4,5-Diphosphate/metabolism

KW - SALM1

KW - Synapses/metabolism

KW - neurexin

KW - synapse organization

KW - synaptogenesis

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DO - https://doi.org/10.15252/embj.2018101289

M3 - Article

C2 - 31368584

SN - 0261-4189

VL - 38

SP - 1

EP - 20

JO - EMBO Journal

JF - EMBO Journal

IS - 17

M1 - e101289

ER -

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

Abstract

Keywords

UN SDGs

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