RRC ID 75933
Author Cizeron M, Granger L, Bülow HE, Bessereau JL.
Title Specific heparan sulfate modifications stabilize the synaptic organizer MADD-4/Punctin at Caenorhabditis elegans neuromuscular junctions.
Journal Genetics
Abstract Heparan sulfate (HS) proteoglycans contribute to the structural organization of various neurochemical synapses. Depending on the system, their role involves either the core protein or the glycosaminoglycan chains. These linear sugar chains are extensively modified by HS modification enzymes, resulting in highly diverse molecules. Specific modifications of glycosaminoglycan chains may thus contribute to a sugar code involved in synapse specificity. Caenorhabditis elegans is particularly useful to address this question because of the low level of genomic redundancy of these enzymes, as opposed to mammals. Here, we systematically mutated the genes encoding HS modification enzymes in C. elegans and analyzed their impact on excitatory and inhibitory neuromuscular junctions (NMJs). Using single chain antibodies that recognize different HS modification patterns, we show in vivo that these two HS epitopes are carried by the SDN-1 core protein, the unique C. elegans syndecan ortholog, at NMJs. Intriguingly, these antibodies differentially bind to excitatory and inhibitory synapses, implying unique HS modification patterns at different NMJs. Moreover, while most enzymes are individually dispensable for proper organization of NMJs, we show that 3-O-sulfation of SDN-1 is required to maintain wild-type levels of the extracellular matrix protein MADD-4/Punctin, a central synaptic organizer that defines the identity of excitatory and inhibitory synaptic domains at the plasma membrane of muscle cells.
Volume 218(4)
Published 2021-8-9
DOI 10.1093/genetics/iyab073
PII 6275221
PMID 33983408
PMC PMC8864735
MeSH Animals Caenorhabditis elegans Caenorhabditis elegans Proteins / metabolism* Heparitin Sulfate / metabolism* Nerve Tissue Proteins / metabolism* Neuromuscular Junction / metabolism* Protein Processing, Post-Translational* Protein Stability Syndecans / metabolism
Resource
C.elegans tm472 tm734 tm3006