TY - JOUR
T1 - The hspg syndecan is a core organizer of cholinergic synapses
AU - Zhou, Xin
AU - Vachon, Camille
AU - Cizeron, Mélissa
AU - Romatif, Océane
AU - Bülow, Hannes E.
AU - Jospin, Maëlle
AU - Bessereau, Jean Louis
N1 - Funding Information:
The Caenorhabditis Genetic Center is funded by the National Institutes of Health Office of Research Infrastructure Programs (grant P40 OD010440). This work was supported by the European Research Council (ERC_Adg C.NAPSE 695295) within the framework of the Université de Lyon LABEX CORTEX (ANR-11-LABX-0042) within the program “Investissements d’Avenir” operated by the French National Research Agency (grant ANR-11-IDEX-0007). Work in the Bülow laboratory is supported by the National Institutes of Health (grants R21NS111145, R01NS096672, and U01CA241981). The authors declare no competing financial interests.
Publisher Copyright:
© 2021 Zhou et al.
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
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U2 - 10.1083/jcb.202011144
DO - 10.1083/jcb.202011144
M3 - Article
C2 - 34213535
AN - SCOPUS:85111793913
VL - 220
JO - Journal of Cell Biology
JF - Journal of Cell Biology
SN - 0021-9525
IS - 9
M1 - e202011144
ER -