Linked Life Data

18534981

Source:http://linkedlifedata.com/resource/pubmed/id/18534981

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
32
pubmed:dateCreated
2008-8-4
pubmed:abstractText
A mutation in the alpha1-subunit (A322D) of GABA(A)Rs is responsible for juvenile myoclonic epilepsy in a large Canadian family. Previous work has identified that this mutant affects the cell expression and function of recombinant GABA(A)Rs, expressed in HEK293 cells. Here we have extended these observations by showing that the mutation promotes association with the endoplasmic reticulum chaperone calnexin and accelerates the degradation rate of the subunits approximately 2.5-fold. We also find that the mutation causes the subunit to be degraded largely by a lysosomal-dependent process. Furthermore, we find that the mutation results in receptors that are inserted into the plasma membrane but are more rapidly endocytosed by a dynamin and caveolin1-dependent mechanism. These results suggest that the mutant subunit can form functional receptors, but that these have a shorter lifetime on the plasma membrane.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
8
pubmed:volume
283
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
22043-50
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Mechanisms involved in the reduction of GABAA receptor alpha1-subunit expression caused by the epilepsy mutation A322D in the trafficking-competent receptor.
pubmed:affiliation
Brain Research Centre, University of British Columbia, Vancouver V6T 1Z3, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't