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Originally published as Genetics Published Articles Ahead of Print on July 1, 2007.
Genetics, Vol. 177, 195-204, September 2007, Copyright © 2007
doi:10.1534/genetics.107.074120
Choline Transport and de novo Choline Synthesis Support Acetylcholine Biosynthesis in Caenorhabditis elegans Cholinergic Neurons
Gregory P. Mullen*,
Eleanor A. Mathews*,
Mai H. Vu*,
Jerrod W. Hunter*,
,
Dennis L. Frisby*,1,
Angie Duke*,
Kiely Grundahl*,
Jamie D. Osborne*,
John A. Crowell*,2 and
James B. Rand*,,3
* Program in Molecular, Cell and Developmental Biology, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104 and Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104
3 Corresponding author: Program in Molecular, Cell and Developmental Biology, Oklahoma Medical Research Foundation, 825 NE 13th St., Oklahoma City, OK 73104.
E-mail: james-rand{at}omrf.org
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-1::GFP 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.