Linked Life Data

17182888

Source:http://linkedlifedata.com/resource/pubmed/id/17182888

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2007-3-22
pubmed:abstractText
In central neurons, the cell-surface distribution of cannabinoid receptor subtype-1 (CB(1)) is highly polarized toward axons and is associated with synaptic terminals, in which it is well-positioned to modulate neurotransmitter release. It has been suggested that high levels of constitutive activity mediate CB(1) receptor axonal targeting, leading to domain-specific endocytosis. We have investigated further the mechanisms that underlie CB(1) receptor axonal polarization in hippocampal neurons and found that constitutive activity is not an essential requirement for this process. We demonstrate that the cell-surface distribution of an N-terminally tagged, fluorescent CB(1) receptor fusion-protein is almost exclusively localized to the axon when expressed in cultured hippocampal neurons. Inhibition of endocytosis by cotransfection with a dominant-negative dynamin-1 (K44A) mutant traps both recombinant and endogenous CB(1) receptors at the somatodendritic cell surface. However, this effect could not be mimicked by inhibiting constitutive activity or receptor activation, either by expressing mutant receptors that lack these properties or by treatment with CB(1) receptor antagonists possessing inverse agonist activity. These data are consistent with a revised model in which domain-specific endocytosis regulates the functional polarization of CB(1) receptors, but this process is distinct from constitutive activity.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0026-895X
pubmed:author
pubmed:issnType
Print
pubmed:volume
71
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
976-84
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
An essential role for constitutive endocytosis, but not activity, in the axonal targeting of the CB1 cannabinoid receptor.
pubmed:affiliation
Neurosciences Institute, Division of Pathology and Neuroscience, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD1 9SY, United Kingdom.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't