Linked Life Data

9682010

Source:http://linkedlifedata.com/resource/pubmed/id/9682010

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1998-8-17
pubmed:abstractText
Huntingtin is a cytoplasmic protein that is found in neurons and somatic cells. In patients with Huntington's disease (HD), the NH2-terminal region of huntingtin has an expanded polyglutamine tract. An abnormal protein interaction by mutant huntingtin has been proposed as a mechanism for HD pathogenesis. Huntingtin associates with vesicle membranes and interacts with proteins involved in vesicle trafficking. It is unclear where along vesicle transport pathways wild-type and mutant huntingtins are found and whether polyglutamine expansion affects this localization. To distinguish wild-type and mutant huntingtin, fibroblasts from normals and HD patients with two mutant alleles (homozygotes) were examined. Immunofluorescence confocal microscopy showed that mutant huntingtin localized with clathrin in membranes of the trans Golgi network and in clathrin-coated and noncoated endosomal vesicles in the cytoplasm and along plasma membranes. Separation of organelles in Nycodenz gradients showed that in normal and HD homozygote patient cells, huntingtin was present in membrane fractions enriched in clathrin. Similar results were obtained in fibroblasts from heterozyote juvenile HD patients who had a highly expanded polyglutamine tract in the HD allele. Western blot analysis of membrane fractions from rat brain showed that wild-type huntingtin was present in fractions that contained purified clathrin-coated membranes or a mixture of clathrin-coated and noncoated membranes. Electron microscopy of huntingtin immunoreactivity in rat brain revealed labeling along dendritic plasma membranes in association with clathrin-coated pits and clusters of noncoated endosomal vesicles 40-60 nm in diameter. These data suggest that wild-type and mutant huntingtin can influence vesicle transport in the secretory and endocytic pathways through associations with clathrin-coated vesicles.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0014-4886
pubmed:author
pubmed:copyrightInfo
Copyright 1998 Academic Press.
pubmed:issnType
Print
pubmed:volume
152
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
34-40
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
Wild-type and mutant huntingtins function in vesicle trafficking in the secretory and endocytic pathways.
pubmed:affiliation
Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, 02114, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't