Source:http://linkedlifedata.com/resource/pubmed/id/21285245
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
Pt 5
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pubmed:dateCreated |
2011-2-15
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pubmed:abstractText |
Ciliopathies represent a newly emerging group of human diseases that share a common etiology resulting from dysfunction of the cilium or centrosome. The gene encoding the retinitis pigmentosa 2 protein (RP2) is mutated in X-linked retinitis pigmentosa. RP2 localizes to the ciliary base and this requires the dual acylation of the N-terminus, but the precise mechanism by which RP2 is trafficked to the cilia is unknown. Here we have characterized an interaction between RP2 and Importin ?2 (transportin-1), a member of the Importin-? family that regulates nuclear-cytoplasmic shuttling. We demonstrate that Importin ?2 is necessary for localization of RP2 to the primary cilium because ablation of Importin ?2 by shRNA blocks entry both of endogenous and exogenous RP2 to the cilium. Furthermore, we identify two distinct binding sites of RP2, which interact independently with Importin ?2. One binding site is a nuclear localization signal (NLS)-like sequence that is located at the N-terminus of RP2 and the other is an M9-like sequence within the tubulin folding cofactor C (TBCC) domain. Mutation of the NLS-like consensus sequence did not abolish localization of RP2 to cilia, suggesting that the sequence is not essential for RP2 ciliary targeting. Interestingly, we found that several missense mutations that cause human disease fall within the M9-like sequence of RP2 and these mutations block entry of RP2 into the cilium, as well as its interaction with Importin ?2. Together, this work further highlights a role of Importin ?2 in regulation of the entry of RP2 and other proteins into the ciliary compartment.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Eye Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Multiprotein Complexes,
http://linkedlifedata.com/resource/pubmed/chemical/RP2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/TNPO1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/beta Karyopherins
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
1477-9137
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:day |
1
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pubmed:volume |
124
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
718-26
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pubmed:meshHeading |
pubmed-meshheading:21285245-Amino Acid Sequence,
pubmed-meshheading:21285245-Animals,
pubmed-meshheading:21285245-Binding Sites,
pubmed-meshheading:21285245-Cell Line,
pubmed-meshheading:21285245-Centrosome,
pubmed-meshheading:21285245-Cilia,
pubmed-meshheading:21285245-Epithelial Cells,
pubmed-meshheading:21285245-Eye Proteins,
pubmed-meshheading:21285245-Gene Knockdown Techniques,
pubmed-meshheading:21285245-Humans,
pubmed-meshheading:21285245-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:21285245-Membrane Proteins,
pubmed-meshheading:21285245-Molecular Sequence Data,
pubmed-meshheading:21285245-Multiprotein Complexes,
pubmed-meshheading:21285245-Recombinant Fusion Proteins,
pubmed-meshheading:21285245-beta Karyopherins
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pubmed:year |
2011
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pubmed:articleTitle |
Localization of retinitis pigmentosa 2 to cilia is regulated by Importin beta2.
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pubmed:affiliation |
Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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