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

The EMBO Journal
Marinka BrouwerMatthijs Verhage

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.

References

Oct 18, 2001·The Journal of Biological Chemistry·T Biederer, T C Sudhof
Aug 31, 2002·Science·Thomas BiedererThomas C Südhof
Jun 11, 2003·Nature Neuroscience·Camin DeanPeter Scheiffele
Jan 25, 2005·Molecular Cell·Venizelos PapayannopoulosWendell A Lim
Feb 1, 2005·Science·Ben ChihPeter Scheiffele
Mar 11, 2005·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Ira MilosevicErwin Neher
May 17, 2005·Molecular and Cellular Neurosciences·Ronald S PetraliaRobert J Wenthold
Feb 24, 2006·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Chang-Yu WangRobert J Wenthold
Jul 15, 2006·Trends in Cell Biology·Tomás Fernández-Alfonso, Timothy A Ryan
Feb 15, 2007·Nature Reviews. Neuroscience·Matthew B DalvaMatthew S Kayser
Mar 16, 2007·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Hiroki TaniguchiPeter Scheiffele
Apr 5, 2007·Nature Protocols·Thomas Biederer, Peter Scheiffele
Oct 16, 2007·Current Opinion in Cell Biology·A Radu Aricescu, E Yvonne Jones
Jan 30, 2008·The Journal of Biological Chemistry·Gail K SeaboldRobert J Wenthold
Oct 14, 2009·Proceedings of the National Academy of Sciences of the United States of America·Mark R EthertonThomas C Südhof
Jan 21, 2010·Physiological Reviews·Juha SaarikangasPekka Lappalainen
Apr 23, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Won MahEunjoon Kim
Dec 15, 2010·Proceedings of the National Academy of Sciences of the United States of America·Yu Fu, Z Josh Huang
Dec 21, 2010·Journal of Neuroscience Methods·Sabine K SchmitzWouter Veldkamp
Oct 25, 2011·Nature·Geert van den BogaartReinhard Jahn
Dec 17, 2011·The Journal of Biological Chemistry·Gail K SeaboldRobert J Wenthold
Nov 7, 2012·Proceedings of the National Academy of Sciences of the United States of America·Seth L Shipman, Roger A Nicoll
Jan 25, 2013·Proceedings of the National Academy of Sciences of the United States of America·Yeong Shin YimJaewon Ko
Sep 11, 2014·Scientific Reports·Luca ChiericoGiuseppe Battaglia
Dec 15, 2015·Nature Reviews. Neuroscience·Joris de Wit, Anirvan Ghosh
Aug 18, 2016·Proceedings of the National Academy of Sciences of the United States of America·Csaba FöldyThomas C Südhof
Dec 3, 2016·Nucleic Acids Research·UNKNOWN The UniProt Consortium
Jan 20, 2018·Nature Communications·Zhaohan LinHeli Liu

❮ Previous
Next ❯

Citations

Jul 16, 2020·Scientific Reports·Sudeep KarkiTommi Kajander
Oct 1, 2021·Communications Biology·Eunkyung LieEunjoon Kim

❮ Previous
Next ❯

Methods Mentioned

BETA
immunoprecipitation
Fluorescence
electron microscopy
cesarean section
transfection
acetylation
PCR
Electrophoresis

Key Resources (RRID) Mentioned

AB_10906317
AB_1310432
AB_2301751
AB_10549720
AB_2566782
AB_1210382
AB_371415
AB_11042617
AB_2572900
AB_2721246

Software Mentioned

iTEM
SPSS
SynD
Polar
ImageJ
GelAnalyzer
SPSS Statistics
MaxQuant
Zeiss LSM510
ImageReader FLA5000

Related Concepts

Related Feeds

Brain developing: Influences & Outcomes

This feed focuses on influences that affect the developing brain including genetics, fetal development, prenatal care, and gene-environment interactions. Here is the latest research in this field.

Cell Adhesion Molecules in the Brain

Cell adhesion molecules found on cell surface help cells bind with other cells or the extracellular matrix to maintain structure and function. Here is the latest research on their role in the brain.

Adhesion Molecules in Health and Disease

Cell adhesion molecules are a subset of cell adhesion proteins located on the cell surface involved in binding with other cells or with the extracellular matrix in the process called cell adhesion. In essence, cell adhesion molecules help cells stick to each other and to their surroundings. Cell adhesion is a crucial component in maintaining tissue structure and function. Discover the latest research on adhesion molecule and their role in health and disease here.