The HSPG syndecan is a core organizer of cholinergic synapses.


Journal

The Journal of cell biology
ISSN: 1540-8140
Titre abrégé: J Cell Biol
Pays: United States
ID NLM: 0375356

Informations de publication

Date de publication:
06 09 2021
Historique:
received: 29 11 2020
revised: 13 04 2021
accepted: 26 05 2021
entrez: 2 7 2021
pubmed: 3 7 2021
medline: 10 11 2021
Statut: ppublish

Résumé

The extracellular matrix has emerged as an active component of chemical synapses regulating synaptic formation, maintenance, and homeostasis. The heparan sulfate proteoglycan (HSPG) syndecans are known to regulate cellular and axonal migration in the brain. They are also enriched at synapses, but their synaptic functions remain more elusive. Here, we show that SDN-1, the sole orthologue of syndecan in C. elegans, is absolutely required for the synaptic clustering of homomeric α7-like acetylcholine receptors (AChRs) and regulates the synaptic content of heteromeric AChRs. SDN-1 is concentrated at neuromuscular junctions (NMJs) by the neurally secreted synaptic organizer Ce-Punctin/MADD-4, which also activates the transmembrane netrin receptor DCC. Those cooperatively recruit the FARP and CASK orthologues that localize α7-like-AChRs at cholinergic NMJs through physical interactions. Therefore, SDN-1 stands at the core of the cholinergic synapse organization by bridging the extracellular synaptic determinants to the intracellular synaptic scaffold that controls the postsynaptic receptor content.

Identifiants

pubmed: 34213535
pii: 212450
doi: 10.1083/jcb.202011144
pmc: PMC8258370
pii:
doi:

Substances chimiques

Angiopoietin-Like Protein 4 0
Caenorhabditis elegans Proteins 0
DCC Receptor 0
MADD-4 protein, C elegans 0
Nerve Tissue Proteins 0
Receptors, Cholinergic 0
Syndecans 0
Guanylate Kinases EC 2.7.4.8
Acetylcholine N9YNS0M02X

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : NIH HHS
ID : P40 OD010440
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS096672
Pays : United States
Organisme : NIH HHS
ID : R21NS111145
Pays : United States
Organisme : NINDS NIH HHS
ID : R21 NS111145
Pays : United States
Organisme : European Research Council
ID : ERC_Adg C.NAPSE 695295
Pays : International
Organisme : NCI NIH HHS
ID : U01 CA241981
Pays : United States

Informations de copyright

© 2021 Zhou et al.

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Auteurs

Xin Zhou (X)

Université de Lyon, Université Claude Bernard Lyon 1, Centre National de la Recherche Scientifique Unite Mixte de Recherche 5310, Institut National de la Santé et de la Recherche Médicale U1217, Institut NeuroMyoGène, Lyon, France.

Camille Vachon (C)

Université de Lyon, Université Claude Bernard Lyon 1, Centre National de la Recherche Scientifique Unite Mixte de Recherche 5310, Institut National de la Santé et de la Recherche Médicale U1217, Institut NeuroMyoGène, Lyon, France.

Mélissa Cizeron (M)

Université de Lyon, Université Claude Bernard Lyon 1, Centre National de la Recherche Scientifique Unite Mixte de Recherche 5310, Institut National de la Santé et de la Recherche Médicale U1217, Institut NeuroMyoGène, Lyon, France.

Océane Romatif (O)

Université de Lyon, Université Claude Bernard Lyon 1, Centre National de la Recherche Scientifique Unite Mixte de Recherche 5310, Institut National de la Santé et de la Recherche Médicale U1217, Institut NeuroMyoGène, Lyon, France.

Hannes E Bülow (HE)

Department of Genetics and Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY.

Maëlle Jospin (M)

Université de Lyon, Université Claude Bernard Lyon 1, Centre National de la Recherche Scientifique Unite Mixte de Recherche 5310, Institut National de la Santé et de la Recherche Médicale U1217, Institut NeuroMyoGène, Lyon, France.

Jean-Louis Bessereau (JL)

Université de Lyon, Université Claude Bernard Lyon 1, Centre National de la Recherche Scientifique Unite Mixte de Recherche 5310, Institut National de la Santé et de la Recherche Médicale U1217, Institut NeuroMyoGène, Lyon, France.

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