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The nonfibrillar multiplexin collagen CLE-1 defines cholinergic synapse identity
 

The nonfibrillar multiplexin collagen CLE-1 defines cholinergic synapse identity

Melissa Cizeron, Anaïs Dumas, Suzanne Le Reun, Laure Granger, Maelle Jospin, Oceane Romatif, Camille Vachon, Delphine Le Guern, Aurore-Cecile Valfort Jean-Louis Bessereau
Science Advances , Vol.11(47)
2025
: 41259523
Animals Caenorhabditis elegans Nerve Tissue Proteins Caenorhabditis elegans Proteins Synapses Neuromuscular Junction Motor Neurons Receptors, Cholinergic Cholinergic Neurons Synaptic Transmission Collagen
Fast neurotransmission requires the coordinated localization of neurotransmitter receptors opposite presynaptic release sites, which usually relies on the transsynaptic interaction of synaptic adhesion molecules. However, some extracellular proteins have been shown to coordinate pre- and postsynaptic differentiation by more elusive mechanisms. Here, we identify the nonfibrillar collagen CLE-1, a member of the evolutionarily conserved multiplexin family, as a master determinant of synapse identity in Caenorhabditis elegans . C. elegans muscle cells are innervated by both cholinergic and GABAergic motoneurons. The CLE-1B isoform is secreted by motoneurons and localizes to neuromuscular junctions. Loss of CLE-1B causes the relocalization of acetylcholine receptors to GABAergic synapses. We show that CLE-1B positions previously unidentified proteolytic fragments of the extracellular scaffold Punctin/MADD-4 to align acetylcholine receptors with cholinergic terminals and independently modulates receptor abundance. These findings reveal CLE-1 as a dual-function synaptic organizer that integrates spatial and quantitative control of postsynaptic receptor localization to maintain synapse identity.

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https://doi.org/10.1126/sciadv.adz1291
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