Linked Life Data

20028484

Source:http://linkedlifedata.com/resource/pubmed/id/20028484

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2010-4-9
pubmed:abstractText
Voltage-gated sodium channels (Na(v)) are essential for the initiation and propagation of action potentials in neurons. Na(v)1.8 activity is regulated by prostaglandin E(2) (PGE(2)). There is, however, no direct evidence showing the regulated trafficking of Na(v)1.8, and the molecular and cellular mechanism of PGE(2)-induced sodium channel trafficking is not clear. Here, we report that PGE(2) regulates the trafficking of Na(v)1.8 through the protein kinase A (PKA) signaling pathway, and an RRR motif in the first intracellular loop of Na(v)1.8 mediates this effect. In rat dorsal root ganglion (DRG) neurons, prolonged PGE(2) treatment enhanced Na(v)1.8 currents by increasing the channel density on the cell surface. Activation of PKA by forskolin had the same effect on DRG neurons and human embryonic kidney 293T cells expressing Na(v)1.8. Inhibition of PKA completely blocked the PGE(2)-promoted effect on Na(v)1.8. Mutation of five PKA phosphorylation sites or the RRR motif in the first intracellular loop of Na(v)1.8 abolished the PKA-promoted Na(v)1.8 surface expression. Furthermore, a membrane-tethered peptide containing the intracellular RRR motif disrupted the PGE(2)-induced promotion of the Na(v)1.8 current in DRG neurons. Our data indicate that PGE(2) promotes the surface expression of Na(v)1.8 via an intracellular RRR motif, and provide a novel mechanism for functional modulation of Na(v)1.8 by hyperalgesic agents.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1600-0854
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
11
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
405-17
pubmed:dateRevised
2010-8-16
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Prostaglandin E2 promotes Na1.8 trafficking via its intracellular RRR motif through the protein kinase A pathway.
pubmed:affiliation
Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, People's Republic of China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't