RRC ID 3608
Author Mullen GP, Mathews EA, Vu MH, Hunter JW, Frisby DL, Duke A, Grundahl K, Osborne JD, Crowell JA, Rand JB.
Title Choline transport and de novo choline synthesis support acetylcholine biosynthesis in Caenorhabditis elegans cholinergic neurons.
Journal Genetics
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.
Volume 177(1)
Pages 195-204
Published 2007-9-1
DOI 10.1534/genetics.107.074120
PII genetics.107.074120
PMID 17603106
PMC PMC2013710
MeSH Acetylcholine / biosynthesis* Adaptation, Physiological Animals Animals, Genetically Modified Caenorhabditis elegans / cytology Caenorhabditis elegans / embryology Caenorhabditis elegans / physiology* Caenorhabditis elegans Proteins Choline / pharmacokinetics* Fluorescent Antibody Technique Membrane Transport Proteins / genetics Membrane Transport Proteins / metabolism* Neurons / cytology Neurons / metabolism* Synapses / metabolism* Synaptic Transmission Tissue Distribution
IF 4.015
Times Cited 15
C.elegans tm373