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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
34
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pubmed:dateCreated |
2009-8-27
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pubmed:abstractText |
Impaired ciliary protein transport in olfactory sensory neurons (OSNs) leads to anosmia, and is a newly recognized clinical manifestation of a class of human disorders called ciliopathies. Surprisingly little is known regarding the mechanisms controlling trafficking to this unique neuronal compartment. Here, we show a novel role for phosphofurin acidic cluster-sorting protein 1 (PACS-1) in the ciliary trafficking of the olfactory cyclic-nucleotide-gated (CNG) channel. PACS-1 is an intracellular sorting protein that mediates its effects through the binding of acidic clusters on cargo protein. This interaction is dependent on CK2 phosphorylation of both PACS-1 and its cargo. We show that CNGB1b contains two putative PACS-1 binding sites, which are phosphorylated by the serine/threonine protein kinase, CK2. Additionally, we show that PACS-1 is expressed in OSNs and interacts in complex with the CNG channel. CK2 inhibition in native OSNs causes a loss of CNG channel from cilia and subsequent olfactory dysfunction, while adenoviral expression of mutant PACS-1 causes similar mislocalization. These results provide a mechanism for the subunit-dependent ciliary trafficking of the CNG channel and offer insight into the mechanisms of ciliary transport.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/19710307-11036268,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19710307-11331585,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19710307-11502258,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19710307-12453462,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19710307-12495842,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19710307-14527438,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19710307-14633983,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19710307-14984756,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19710307-15137945,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19710307-15174942,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19710307-15322545,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19710307-15634774,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19710307-15692563,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19710307-15723066,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19710307-16308564,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19710307-16481400,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19710307-16537653,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19710307-16740644,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19710307-16782012,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19710307-16943304,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19710307-16977309,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19710307-16980309,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19710307-17898177,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19710307-19505291,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19710307-8186392,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19710307-8846780
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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/4,5,6,7-tetrabromobenzotriazole,
http://linkedlifedata.com/resource/pubmed/chemical/Alanine,
http://linkedlifedata.com/resource/pubmed/chemical/Casein Kinase II,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic Nucleotide-Gated Cation...,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Green Fluorescent Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/PACS1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Subunits,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Serine,
http://linkedlifedata.com/resource/pubmed/chemical/Triazoles,
http://linkedlifedata.com/resource/pubmed/chemical/Vesicular Transport Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
1529-2401
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
26
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pubmed:volume |
29
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
10541-51
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pubmed:dateRevised |
2011-8-1
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pubmed:meshHeading |
pubmed-meshheading:19710307-Alanine,
pubmed-meshheading:19710307-Animals,
pubmed-meshheading:19710307-Casein Kinase II,
pubmed-meshheading:19710307-Cell Line, Transformed,
pubmed-meshheading:19710307-Cilia,
pubmed-meshheading:19710307-Cyclic Nucleotide-Gated Cation Channels,
pubmed-meshheading:19710307-Dogs,
pubmed-meshheading:19710307-Enzyme Inhibitors,
pubmed-meshheading:19710307-Green Fluorescent Proteins,
pubmed-meshheading:19710307-Humans,
pubmed-meshheading:19710307-Immunoprecipitation,
pubmed-meshheading:19710307-Mice,
pubmed-meshheading:19710307-Mice, Transgenic,
pubmed-meshheading:19710307-Mutation,
pubmed-meshheading:19710307-Olfactory Mucosa,
pubmed-meshheading:19710307-Phosphorylation,
pubmed-meshheading:19710307-Protein Subunits,
pubmed-meshheading:19710307-Protein Transport,
pubmed-meshheading:19710307-RNA, Messenger,
pubmed-meshheading:19710307-RNA Interference,
pubmed-meshheading:19710307-Sensory Receptor Cells,
pubmed-meshheading:19710307-Serine,
pubmed-meshheading:19710307-Transfection,
pubmed-meshheading:19710307-Triazoles,
pubmed-meshheading:19710307-Vesicular Transport Proteins
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pubmed:year |
2009
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pubmed:articleTitle |
PACS-1 mediates phosphorylation-dependent ciliary trafficking of the cyclic-nucleotide-gated channel in olfactory sensory neurons.
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pubmed:affiliation |
Department of Pharmacology, University of Michigan, Ann Arbor, Michigan 48109-5632, USA.
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