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The Journal of Neuroscience, May 1, 2003, 23(9):3577

The Basement Membrane Components Nidogen and Type XVIII Collagen Regulate Organization of Neuromuscular Junctions in Caenorhabditis elegans

Brian D. Ackley^{1, 2, 3}, Seong Hoon Kang¹, Jennifer R. Crew¹, Chris Suh³, Yishi Jin^{2, 3}, and James M. Kramer¹

¹ Department of Cell and Molecular Biology, Northwestern University Medical School, Chicago, Illinois 60611, and ² Howard Hughes Medical Institute, and ³ Department of Molecular, Cellular, and Developmental Biology, University of California Santa Cruz, Santa Cruz, California 95064

Vertebrate neuromuscular junctions (NMJs) contain specialized basal laminas enriched for proteins not found at high concentrations extrasynaptically. Alterations in NMJ basement membrane components can result in loss of NMJ structural integrity and lead to muscular dystrophies. We demonstrate here that the conserved Caenorhabditis elegans basement membrane-associated molecules nidogen/entactin (NID-1) and type XVIII collagen (CLE-1) are associated with axons and particularly enriched near synaptic contacts. NID-1 is concentrated laterally, between the nerve cord and muscles, whereas CLE-1 is concentrated dorsal to the ventral nerve cord and ventral to the dorsal nerve cord, above the regions where synapses form. Mutations in these molecules cause specific and distinct defects in the organization of neuromuscular junctions. The mutant animals exhibit mild movement defects and altered responses to an inhibitor of acetylcholinesterase and a cholinergic agonist, indicating altered synaptic function. Our results provide the first demonstration that basement membrane molecules are important for NMJ formation and/or maintenance in C. elegans and that collagen XVIII and nidogen can have important roles in synapse organization.

Key words: synaptogenesis; neuromuscular junction; extracellular matrix; collagen XVIII; nidogen; Caenorhabditis elegans

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Copyright © 2003 Society for Neuroscience  0270-6474/03/2393577-11$05.00/0

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