rdf:type |
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lifeskim:mentions |
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pubmed:issue |
13
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pubmed:dateCreated |
1998-3-18
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pubmed:databankReference |
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pubmed:abstractText |
Huntington's disease (HD) is an inherited neurodegenerative disease caused by expansion of a polyglutamine repeat in the HD protein huntingtin. Huntingtin's localization within the cell includes an association with cytoskeletal elements and vesicles. We previously identified a protein (HAP1) which binds to huntingtin in a glutamine repeat length-dependent manner. We now report that HAP1 interacts with cytoskeletal proteins, namely the p150 Glued subunit of dynactin and the pericentriolar protein PCM-1. Structural predictions indicate that both HAP1 and the interacting proteins have a high probability of forming coiled coils. We examined the interaction of HAP1 with p150 Glued . Binding of HAP1 to p150 Glued (amino acids 879-1150) was confirmed in vitro by binding of p150 Glued to a HAP1-GST fusion protein immobilized on glutathione-Sepharose beads. Also, HAP1 co-immunoprecipitated with p150 Glued from brain extracts, indicating that the interaction occurs in vivo . Like HAP1, p150 Glued is highly expressed in neurons in brain and both proteins are enriched in a nerve terminal vesicle-rich fraction. Double label immunofluorescence experiments in NGF-treated PC12 cells using confocal microscopy revealed that HAP1 and p150 Glued partially co-localize. These results suggest that HAP1 might function as an adaptor protein using coiled coils to mediate interactions among cytoskeletal, vesicular and motor proteins. Thus, HAP1 and huntingtin may play a role in vesicle trafficking within the cell and disruption of this function could contribute to the neuronal dysfunction and death seen in HD.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/APEX1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Apex1 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Autoantigens,
http://linkedlifedata.com/resource/pubmed/chemical/Carbon-Oxygen Lyases,
http://linkedlifedata.com/resource/pubmed/chemical/Cell Cycle Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/DNA, Complementary,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-(Apurinic or Apyrimidinic...,
http://linkedlifedata.com/resource/pubmed/chemical/Kinesin,
http://linkedlifedata.com/resource/pubmed/chemical/Macromolecular Substances,
http://linkedlifedata.com/resource/pubmed/chemical/Microtubule-Associated Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/PCM1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/dynactin
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0964-6906
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pubmed:author |
|
pubmed:issnType |
Print
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pubmed:volume |
6
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2205-12
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pubmed:dateRevised |
2011-8-4
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pubmed:meshHeading |
pubmed-meshheading:9361024-Animals,
pubmed-meshheading:9361024-Autoantigens,
pubmed-meshheading:9361024-Base Sequence,
pubmed-meshheading:9361024-Brain Chemistry,
pubmed-meshheading:9361024-Carbon-Oxygen Lyases,
pubmed-meshheading:9361024-Cell Cycle Proteins,
pubmed-meshheading:9361024-Cell Line,
pubmed-meshheading:9361024-Chromatography, Affinity,
pubmed-meshheading:9361024-Cytoskeleton,
pubmed-meshheading:9361024-DNA, Complementary,
pubmed-meshheading:9361024-DNA-(Apurinic or Apyrimidinic Site) Lyase,
pubmed-meshheading:9361024-Humans,
pubmed-meshheading:9361024-Kinesin,
pubmed-meshheading:9361024-Macromolecular Substances,
pubmed-meshheading:9361024-Microscopy, Confocal,
pubmed-meshheading:9361024-Microtubule-Associated Proteins,
pubmed-meshheading:9361024-Molecular Sequence Data,
pubmed-meshheading:9361024-Nuclear Proteins,
pubmed-meshheading:9361024-PC12 Cells,
pubmed-meshheading:9361024-Protein Binding,
pubmed-meshheading:9361024-Protein Conformation,
pubmed-meshheading:9361024-Rats,
pubmed-meshheading:9361024-Recombinant Fusion Proteins,
pubmed-meshheading:9361024-Saccharomyces cerevisiae
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pubmed:year |
1997
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pubmed:articleTitle |
Huntingtin-associated protein 1 (HAP1) interacts with the p150Glued subunit of dynactin.
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pubmed:affiliation |
Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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