title: Choline transport and de novo choline synthesis support acetylcholine biosynthesis in Caenorhabditis elegans cholinergic neurons.
abstract: The cho-1 gene in Caenorhabditis elegans encodes a high-affinity plasma-membrane choline transporter believed to be rate limiting for acetylcholine (ACh) synthesis in cholinergic nerve terminals. We found that CHO-1 is expressed in most, but not all cholinergic neurons in C. elegans. cho-1 null mutants are viable and exhibit mild deficits in cholinergic behavior; they are slightly resistant to the acetylcholinesterase inhibitor aldicarb, and they exhibit reduced swimming rates in liquid. cho-1 mutants also fail to sustain swimming behavior; over a 33-min time course, cho-1 mutants slow down or stop swimming, whereas wild-type animals sustain the initial rate of swimming over the duration of the experiment. A functional CHO-1GFP fusion protein rescues these cho-1 mutant phenotypes and is enriched at cholinergic synapses. Although cho-1 mutants clearly exhibit defects in cholinergic behaviors, the loss of cho-1 function has surprisingly mild effects on cholinergic neurotransmission. However, reducing endogenous choline synthesis strongly enhances the phenotype of cho-1 mutants, giving rise to a synthetic uncoordinated phenotype. Our results indicate that both choline transport and de novo synthesis provide choline for ACh synthesis in C. elegans cholinergic neurons.
authors.affiliation: Program in Molecular, Cell and Developmental Biology, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104, USA.
authors.forename: Gregory P
authors.initials: GP
authors.lastname: Mullen
authors.forename: Eleanor A
authors.initials: EA
authors.lastname: Mathews
authors.forename: Mai H
authors.initials: MH
authors.lastname: Vu
authors.forename: Jerrod W
authors.initials: JW
authors.lastname: Hunter
authors.forename: Dennis L
authors.initials: DL
authors.lastname: Frisby
authors.forename: Angie
authors.initials: A
authors.lastname: Duke
authors.forename: Kiely
authors.initials: K
authors.lastname: Grundahl
authors.forename: Jamie D
authors.initials: JD
authors.lastname: Osborne
authors.forename: John A
authors.initials: JA
authors.lastname: Crowell
authors.forename: James B
authors.initials: JB
authors.lastname: Rand
mesh_terms: D000109:Acetylcholine / Q000096:biosynthesis*; D000222:Adaptation, Physiological; D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000166:cytology / Q000196:embryology / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins; D002794:Choline / Q000493:pharmacokinetics*; D005455:Fluorescent Antibody Technique; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism*; D009435:Synaptic Transmission; D014018:Tissue Distribution
chemical_list: D029742:Caenorhabditis elegans Proteins; D026901:Membrane Transport Proteins; C065637:choline transporter; D002794:Choline; D000109:Acetylcholine