The Ror receptor tyrosine kinase CAM-1 is required for ACR-16-mediated synaptic transmission at the C. elegans neuromuscular junction.
Nicotinic (cholinergic) neurotransmission plays a critical role in the vertebrate nervous system, underlies nicotine addiction, and nicotinic receptor dysfunction leads to neurological disorders. The C. elegans neuromuscular junction (NMJ) shares many characteristics with neuronal synapses, including multiple classes of postsynaptic currents. Here, we identify two genes required for the major excitatory current found at the C. elegans NMJ: acr-16, which encodes a nicotinic AChR subunit homologous to the vertebrate alpha7 subunit, and cam-1, which encodes a Ror receptor tyrosine kinase. acr-16 mutants lack fast cholinergic current at the NMJ and exhibit synthetic behavioral deficits with other known AChR mutants. In cam-1 mutants, ACR-16 is mislocalized and ACR-16-dependent currents are disrupted. The postsynaptic deficit in cam-1 mutants is accompanied by alterations in the distribution of cholinergic vesicles and associated synaptic proteins. We hypothesize that CAM-1 contributes to the localization or stabilization of postsynaptic ACR-16 receptors and presynaptic release sites.
Francis
Michael M
MM
Department of Biology, University of Utah, Salt Lake City 84112, USA.
Evans
Susan P
SP
Jensen
Michael
M
Madsen
David M
DM
Mancuso
Joel
J
Norman
Kenneth R
KR
Maricq
Andres Villu
AV
D000109:Acetylcholine / Q000378:metabolism / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D030801:Animals, Genetically Modified; D001522:Behavior, Animal; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000145:classification / Q000235:genetics / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D002794:Choline / Q000494:pharmacology; D018680:Cholinergic Antagonists / Q000494:pharmacology; D003952:Diagnostic Imaging; D004079:Dihydro-beta-Erythroidine / Q000494:pharmacology; D004558:Electric Stimulation / Q000379:methods; D005786:Gene Expression Regulation / Q000235:genetics; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D007978:Levamisole / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects; D046529:Microscopy, Electron, Transmission / Q000379:methods; D008967:Molecular Biology; D009068:Movement / Q000502:physiology; D009132:Muscles / Q000187:drug effects / Q000502:physiology; D016296:Mutagenesis; D009154:Mutation; D009469:Neuromuscular Junction / Q000187:drug effects / Q000378:metabolism*; D009474:Neurons / Q000502:physiology; D009538:Nicotine / Q000494:pharmacology; D018408:Patch-Clamp Techniques / Q000379:methods; D034741:RNA, Small Interfering; D020794:Receptor Protein-Tyrosine Kinases / Q000502:physiology*; D057050:Receptor Tyrosine Kinase-like Orphan Receptors; D011978:Receptors, Nicotinic / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D013572:Synaptic Vesicles / Q000378:metabolism / Q000648:ultrastructure; D013997:Time Factors; D015534:Trans-Activators / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D029742:Caenorhabditis elegans Proteins; D018680:Cholinergic Antagonists; D034741:RNA, Small Interfering; D011978:Receptors, Nicotinic; D015534:Trans-Activators; C099378:acr-16 protein, C elegans; D004079:Dihydro-beta-Erythroidine; D007978:Levamisole; D005680:gamma-Aminobutyric Acid; D009538:Nicotine; C526267:CAM-1 protein, C elegans; D020794:Receptor Protein-Tyrosine Kinases; D057050:Receptor Tyrosine Kinase-like Orphan Receptors; D002794:Choline; D000109:Acetylcholine; D002118:Calcium