Linked Life Data

17200151

Source:http://linkedlifedata.com/resource/pubmed/id/17200151

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2007-2-5
pubmed:abstractText
Myoclonus-dystonia syndrome (MDS) is a genetically heterogeneous disorder characterized by myoclonic jerks often seen in combination with dystonia and psychiatric co-morbidities and epilepsy. Mutations in the gene encoding epsilon-sarcoglycan (SGCE) have been found in some patients with MDS. SGCE is a maternally imprinted gene with the disease being inherited in an autosomal dominant pattern with reduced penetrance upon maternal transmission. In the central nervous system, epsilon-sarcoglycan is widely expressed in neurons of the cerebral cortex, basal ganglia, hippocampus, cerebellum and the olfactory bulb. epsilon-Sarcoglycan is located at the plasma membrane in neurons, muscle and transfected cells. To determine the effect of MDS-associated mutations on the function of epsilon-sarcoglycan we examined the biosynthesis and trafficking of wild-type and mutant proteins in cultured cells. In contrast to the wild-type protein, disease-associated epsilon-sarcoglycan missense mutations (H36P, H36R and L172R) produce proteins that are undetectable at the cell surface and are retained intracellularly. These mutant proteins become polyubiquitinated and are rapidly degraded by the proteasome. Furthermore, torsinA, that is mutated in DYT1 dystonia, a rare type of primary dystonia, binds to and promotes the degradation of epsilon-sarcoglycan mutants when both proteins are co-expressed. These data demonstrate that some MDS-associated mutations in SGCE impair trafficking of the mutant protein to the plasma membrane and suggest a role for torsinA and the ubiquitin proteasome system in the recognition and processing of misfolded epsilon-sarcoglycan.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0964-6906
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
16
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
327-42
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:17200151-Animals, pubmed-meshheading:17200151-COS Cells, pubmed-meshheading:17200151-Cell Membrane, pubmed-meshheading:17200151-Cells, Cultured, pubmed-meshheading:17200151-Cercopithecus aethiops, pubmed-meshheading:17200151-Dystonic Disorders, pubmed-meshheading:17200151-Embryo, Mammalian, pubmed-meshheading:17200151-Humans, pubmed-meshheading:17200151-Mice, pubmed-meshheading:17200151-Molecular Chaperones, pubmed-meshheading:17200151-Mutant Proteins, pubmed-meshheading:17200151-Mutation, Missense, pubmed-meshheading:17200151-Myoclonus, pubmed-meshheading:17200151-Protein Processing, Post-Translational, pubmed-meshheading:17200151-Protein Transport, pubmed-meshheading:17200151-Rats, pubmed-meshheading:17200151-Sarcoglycans, pubmed-meshheading:17200151-Syndrome, pubmed-meshheading:17200151-Ubiquitin
pubmed:year
2007
pubmed:articleTitle
SGCE missense mutations that cause myoclonus-dystonia syndrome impair epsilon-sarcoglycan trafficking to the plasma membrane: modulation by ubiquitination and torsinA.
pubmed:affiliation
Department of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3QT, UK.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't