|
rdf:type |
|
|
lifeskim:mentions |
umls-concept:C0026046,
umls-concept:C0027882,
umls-concept:C0038952,
umls-concept:C0107103,
umls-concept:C0183683,
umls-concept:C0344211,
umls-concept:C1171411,
umls-concept:C1317973,
umls-concept:C1325417,
umls-concept:C1415504,
umls-concept:C1521721,
umls-concept:C1999177,
umls-concept:C2587213
|
|
pubmed:issue |
1
|
|
pubmed:dateCreated |
2004-7-9
|
|
pubmed:abstractText |
Polyglutamine expansion (polyQ) in the protein huntingtin is pathogenic and responsible for the neuronal toxicity associated with Huntington's disease (HD). Although wild-type huntingtin possesses antiapoptotic properties, the relationship between the neuroprotective functions of huntingtin and pathogenesis of HD remains unclear. Here, we show that huntingtin specifically enhances vesicular transport of brain-derived neurotrophic factor (BDNF) along microtubules. Huntingtin-mediated transport involves huntingtin-associated protein-1 (HAP1) and the p150(Glued) subunit of dynactin, an essential component of molecular motors. BDNF transport is attenuated both in the disease context and by reducing the levels of wild-type huntingtin. The alteration of the huntingtin/HAP1/p150(Glued) complex correlates with reduced association of motor proteins with microtubules. Finally, we find that the polyQ-huntingtin-induced transport deficit results in the loss of neurotrophic support and neuronal toxicity. Our findings indicate that a key role of huntingtin is to promote BDNF transport and suggest that loss of this function might contribute to pathogenesis.
|
|
pubmed:grant |
|
|
pubmed:commentsCorrections |
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Jul
|
|
pubmed:issn |
0092-8674
|
|
pubmed:author |
pubmed-author:Borrell-PagèsMariaM,
pubmed-author:CharrinBénédicte CBC,
pubmed-author:CordelièresFabrice PFP,
pubmed-author:De MeyJanJ,
pubmed-author:DompierreJim PJP,
pubmed-author:GauthierLaurent RLR,
pubmed-author:HumbertSandrineS,
pubmed-author:LessmannVolkmarV,
pubmed-author:MacDonaldMarcy EME,
pubmed-author:RangoneHélèneH,
pubmed-author:SaudouFrédéricF
|
|
pubmed:issnType |
Print
|
|
pubmed:day |
9
|
|
pubmed:volume |
118
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
127-38
|
|
pubmed:dateRevised |
2007-11-14
|
|
pubmed:meshHeading |
pubmed-meshheading:15242649-Animals,
pubmed-meshheading:15242649-Biological Transport,
pubmed-meshheading:15242649-Brain,
pubmed-meshheading:15242649-Brain-Derived Neurotrophic Factor,
pubmed-meshheading:15242649-Cell Survival,
pubmed-meshheading:15242649-Cells, Cultured,
pubmed-meshheading:15242649-Cytoplasmic Vesicles,
pubmed-meshheading:15242649-DNA-Binding Proteins,
pubmed-meshheading:15242649-Mice,
pubmed-meshheading:15242649-Microtubule-Associated Proteins,
pubmed-meshheading:15242649-Microtubules,
pubmed-meshheading:15242649-Models, Biological,
pubmed-meshheading:15242649-Nerve Tissue Proteins,
pubmed-meshheading:15242649-Neurons,
pubmed-meshheading:15242649-Nuclear Proteins
|
|
pubmed:year |
2004
|
|
pubmed:articleTitle |
Huntingtin controls neurotrophic support and survival of neurons by enhancing BDNF vesicular transport along microtubules.
|
|
pubmed:affiliation |
Unité Mixte de Recherche 146, Centre National de la Recherche Scientifique, Institut Curie, Building 110, Centre Universitaire, 91405 Orsay Cedex, France.
|
|
pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
|
