An extracellular complex between CLE-1/collagen XV/XVIII and Punctin/MADD-4 defines cholinergic synapse identity

Cizeron, M.; Dumas, A.; Le Reun, S.; Granger, L.; Jospin, M.; Romatif, O.; Vachon, C.; Le Guern, D.; Valfort, A.-C.; Bessereau, J.-L.

doi:10.1101/2025.03.26.645569

bioRxiv · 10.1101/2025.03.26.645569

An extracellular complex between CLE-1/collagen XV/XVIII and Punctin/MADD-4 defines cholinergic synapse identity

Cizeron, M.·Dumas, A.·Le Reun, S.·Granger, L.·Jospin, M.·Romatif, O.·Vachon, C.·Le Guern, D.·Valfort, A.-C.·Bessereau, J.-L.

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Abstract

The precise localization of postsynaptic receptors opposite neurotransmitter release sites is essential for synaptic function. This alignment relies on adhesion molecules, intracellular scaffolds, and a growing class of extracellular scaffolding proteins. However, how these secreted proteins are retained at synapses remains unclear. We addressed this question using C. elegans neuromuscular junctions, where Punctin, a conserved extracellular synaptic organizer, positions postsynaptic receptors. We identified CLE-1, the ortholog of collagens XV/XVIII, as a key stabilizer of Punctin. Punctin and CLE-1B, the main isoform present at neuromuscular junctions, form a complex and rely on each other for synaptic localization. Punctin undergoes cleavage, and in the absence of CLE-1, specific fragments are lost, resulting in the mislocalization of cholinergic receptors to GABAergic synapses. Additionally, CLE-1 regulates receptor levels independently of Punctin. These findings highlight a crucial extracellular complex that maintains synapse identity.

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Cizeron, M., Dumas, A., Le Reun, S., Granger, L., Jospin, M., Romatif, O., Vachon, C., Le Guern, D., Valfort, A.-C., Bessereau, J.-L.. 2025-03-30. An extracellular complex between CLE-1/collagen XV/XVIII and Punctin/MADD-4 defines cholinergic synapse identity. https://doi.org/10.1101/2025.03.26.645569

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