التفاصيل البيبلوغرافية
| العنوان: |
PACS-1 Mediates Phosphorylation-Dependent Ciliary Trafficking of the Cyclic-Nucleotide-Gated Channel in Olfactory Sensory Neurons. |
| المؤلفون: |
Jenkins, Paul M.1, Lian Zhang1, Thomas, Gary2, Martens, Jeffrey R.1 martensj@umich.edu |
| المصدر: |
Journal of Neuroscience. 8/26/2009, Vol. 29 Issue 34, p10541-10551. 11p. 7 Diagrams. |
| مصطلحات موضوعية: |
*PHOSPHORYLATION, *CILIARY ganglion, *CYCLIC nucleotides, *OLFACTORY nerve, *SENSORY neurons, *PROTEIN kinases, *DISEASES |
| مستخلص: |
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. [ABSTRACT FROM AUTHOR] |
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