The basement membrane components nidogen and type XVIII collagen regulate organization of neuromuscular junctions in Caenorhabditis elegans.
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.
Department of Cell and Molecular Biology, Northwestern University Medical School, Chicago, Illinois 60611, USA.
Brian D
BD
Ackley
Seong Hoon
SH
Kang
Jennifer R
JR
Crew
Chris
C
Suh
Yishi
Y
Jin
James M
JM
Kramer
D000483:Alleles; D000818:Animals; D001485:Basement Membrane / Q000378:metabolism*; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D002135:Calcium-Binding Proteins; D018679:Cholinergic Agonists / Q000494:pharmacology; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D003094:Collagen / Q000235:genetics / Q000378:metabolism*; D043170:Collagen Type XVIII; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins; D008164:Luminescent Proteins / Q000096:biosynthesis / Q000235:genetics; D008562:Membrane Glycoproteins / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D009043:Motor Activity / Q000187:drug effects / Q000235:genetics; D009069:Movement Disorders / Q000235:genetics; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000096:biosynthesis; D009420:Nervous System / Q000503:physiopathology; D009421:Nervous System Malformations / Q000235:genetics; D009469:Neuromuscular Junction / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism; D050857:Synaptotagmins; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D029742:Caenorhabditis elegans Proteins; D002135:Calcium-Binding Proteins; D018679:Cholinergic Agonists; D002800:Cholinesterase Inhibitors; D043170:Collagen Type XVIII; D008164:Luminescent Proteins; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; C029967:nidogen; D050857:Synaptotagmins; D049452:Green Fluorescent Proteins; D005680:gamma-Aminobutyric Acid; D003094:Collagen