RRC ID |
3608
|
著者 |
Mullen GP, Mathews EA, Vu MH, Hunter JW, Frisby DL, Duke A, Grundahl K, Osborne JD, Crowell JA, Rand JB.
|
タイトル |
Choline transport and de novo choline synthesis support acetylcholine biosynthesis in Caenorhabditis elegans cholinergic neurons.
|
ジャーナル |
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.
|
巻・号 |
177(1)
|
ページ |
195-204
|
公開日 |
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
|
引用数 |
15
|
WOS 分野
|
GENETICS & HEREDITY
|
リソース情報 |
線虫 |
tm373 |