Choline transport and de novo choline synthesis support acetylcholine biosynthesis in Caenorhabditis elegans cholinergic neurons.
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.
Mullen
Gregory P
GP
Program in Molecular, Cell and Developmental Biology, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104, USA.
Mathews
Eleanor A
EA
Vu
Mai H
MH
Hunter
Jerrod W
JW
Frisby
Dennis L
DL
Duke
Angie
A
Grundahl
Kiely
K
Osborne
Jamie D
JD
Crowell
John A
JA
Rand
James B
JB
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
D029742:Caenorhabditis elegans Proteins; D026901:Membrane Transport Proteins; C065637:choline transporter; D002794:Choline; D000109:Acetylcholine