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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
11
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pubmed:dateCreated |
2008-11-3
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pubmed:abstractText |
Synaptic proteins are synthesized in the cell body and transported down the axon by microtubule-dependent motors. We previously reported that KIF1Bbeta and KIF1A motors are essential for transporting synaptic vesicle precursors; however the mechanisms that regulate transport, as well as cargo recognition and control of cargo loading and unloading remain largely unknown. Here, we show that DENN/MADD (Rab3-GEP) is an essential part of the regulation mechanism through direct interaction with the stalk domain of KIF1Bbeta and KIF1A. We also show that DENN/MADD binds preferentially to GTP-Rab3 and acts as a Rab3 effector. These molecular interactions are fundamental as sequential genetic perturbations revealed that KIF1Bbeta and KIF1A are essential for the transport of DENN/MADD and Rab3, whereas DENN/MADD is essential for the transport of Rab3. GTP-Rab3 was more effectively transported than GDP-Rab3, suggesting that the nucleotide state of Rab3 regulates axonal transport of Rab3-carrying vesicles through preferential interaction with DENN/MADD.
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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/Death Domain Receptor Signaling...,
http://linkedlifedata.com/resource/pubmed/chemical/Glutathione Transferase,
http://linkedlifedata.com/resource/pubmed/chemical/Guanine Nucleotide Exchange Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Guanosine Triphosphate,
http://linkedlifedata.com/resource/pubmed/chemical/KIF11 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/KIF1A protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Kinesin,
http://linkedlifedata.com/resource/pubmed/chemical/MADD protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/rab3 GTP-Binding Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
1476-4679
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:volume |
10
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1269-79
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pubmed:meshHeading |
pubmed-meshheading:18849981-Adenoviridae,
pubmed-meshheading:18849981-Axonal Transport,
pubmed-meshheading:18849981-Cell Line,
pubmed-meshheading:18849981-Death Domain Receptor Signaling Adaptor Proteins,
pubmed-meshheading:18849981-Genetic Vectors,
pubmed-meshheading:18849981-Glutathione Transferase,
pubmed-meshheading:18849981-Guanine Nucleotide Exchange Factors,
pubmed-meshheading:18849981-Guanosine Triphosphate,
pubmed-meshheading:18849981-Immunohistochemistry,
pubmed-meshheading:18849981-Kidney,
pubmed-meshheading:18849981-Kinesin,
pubmed-meshheading:18849981-Protein Structure, Tertiary,
pubmed-meshheading:18849981-RNA Interference,
pubmed-meshheading:18849981-Recombinant Proteins,
pubmed-meshheading:18849981-Synaptic Vesicles,
pubmed-meshheading:18849981-Transfection,
pubmed-meshheading:18849981-rab3 GTP-Binding Proteins
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pubmed:year |
2008
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pubmed:articleTitle |
KIF1Bbeta- and KIF1A-mediated axonal transport of presynaptic regulator Rab3 occurs in a GTP-dependent manner through DENN/MADD.
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pubmed:affiliation |
Department of Cell Biology and Anatomy, Graduate School of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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