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The Journal of Neuroscience, August 26, 2009, 29(34):10541-10551; doi:10.1523/JNEUROSCI.1590-09.2009

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Cellular/Molecular
PACS-1 Mediates Phosphorylation-Dependent Ciliary Trafficking of the Cyclic-Nucleotide-Gated Channel in Olfactory Sensory Neurons

Paul M. Jenkins,¹ Lian Zhang,¹ Gary Thomas,² and Jeffrey R. Martens¹

¹Department of Pharmacology, University of Michigan, Ann Arbor, Michigan 48109-5632, and ²Vollum Institute, Oregon Health & Science University, Portland, Oregon 97239

Correspondence should be addressed to Asst. Prof. Jeffrey R. Martens, Department of Pharmacology, University of Michigan, 1150 West Medical Center Drive, 1301 MSRB III, Ann Arbor, MI 48109-5632. Email: martensj{at}umich.edu

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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Received April 1, 2009; revised June 25, 2009; accepted July 20, 2009.

Correspondence should be addressed to Asst. Prof. Jeffrey R. Martens, Department of Pharmacology, University of Michigan, 1150 West Medical Center Drive, 1301 MSRB III, Ann Arbor, MI 48109-5632. Email: martensj{at}umich.edu

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