Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2010-4-13
pubmed:abstractText
Cholinergic neurons rely on the sodium-dependent choline transporter CHT to provide choline for synthesis of acetylcholine. CHT cycles between cell surface and subcellular organelles, but little is known about regulation of this trafficking. We hypothesized that activation of protein kinase C with phorbol ester modulates choline uptake by altering the rate of CHT internalization from or delivery to the plasma membrane. Using SH-SY5Y cells that stably express rat CHT, we found that exposure of cells to phorbol ester for 2 or 5 min significantly increased choline uptake, whereas longer treatment had no effect. Kinetic analysis revealed that 5 min phorbol ester treatment significantly enhanced V(max) of choline uptake, but had no effect on K(m) for solute binding. Cell-surface biotinylation assays showed that plasma membrane levels of CHT protein were enhanced following 5 min phorbol ester treatment; this was blocked by protein kinase C inhibitor bisindolylmaleimide-I. Moreover, CHT internalization was decreased and delivery of CHT to plasma membrane was increased by phorbol ester. Our results suggest that treatment of neural cells with the protein kinase C activator phorbol ester rapidly and transiently increases cell surface CHT levels and this corresponds with enhanced choline uptake activity which may play an important role in replenishing acetylcholine stores following its release by depolarization.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1873-7544
pubmed:author
pubmed:copyrightInfo
Copyright 2010 IBRO. Published by Elsevier Ltd. All rights reserved.
pubmed:issnType
Electronic
pubmed:day
19
pubmed:volume
167
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
765-73
pubmed:meshHeading
pubmed-meshheading:20167259-Acetylcholine, pubmed-meshheading:20167259-Animals, pubmed-meshheading:20167259-Brain, pubmed-meshheading:20167259-Cell Line, Tumor, pubmed-meshheading:20167259-Cell Membrane, pubmed-meshheading:20167259-Endocytosis, pubmed-meshheading:20167259-Enzyme Activation, pubmed-meshheading:20167259-Enzyme Inhibitors, pubmed-meshheading:20167259-Kinetics, pubmed-meshheading:20167259-Membrane Potentials, pubmed-meshheading:20167259-Nerve Tissue Proteins, pubmed-meshheading:20167259-Neurons, pubmed-meshheading:20167259-Phosphorylation, pubmed-meshheading:20167259-Plasma Membrane Neurotransmitter Transport Proteins, pubmed-meshheading:20167259-Protein Kinase C, pubmed-meshheading:20167259-Protein Transport, pubmed-meshheading:20167259-Rats, pubmed-meshheading:20167259-Tetradecanoylphorbol Acetate
pubmed:year
2010
pubmed:articleTitle
Rapid, transient effects of the protein kinase C activator phorbol 12-myristate 13-acetate on activity and trafficking of the rat high-affinity choline transporter.
pubmed:affiliation
Robarts Research Institute, University of Western Ontario, London, Ontario, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't