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PACS‐1 Mediates Phosphorylation‐Dependent Ciliary Trafficking of the CNG Channel in Olfactory Sensory Neurons
Author(s) -
Jenkins Paul Michael,
Zhang Lian,
Thomas Gary,
Martens Jeffrey R.
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.580.6
Subject(s) - cilium , microbiology and biotechnology , cyclic nucleotide gated ion channel , ciliopathies , phosphorylation , olfactory epithelium , olfactory mucosa , anosmia , biology , olfactory system , protein subunit , transport protein , neuroscience , chemistry , biochemistry , medicine , nucleotide , cyclic nucleotide , gene , disease , covid-19 , infectious disease (medical specialty) , phenotype
Ciliopathies are an emerging class of human disorders that involve defects in ciliary protein trafficking or assembly. Although impaired ciliary protein transport in olfactory sensory neurons (OSNs) leads to anosmia, surprisingly little is known regarding the mechanisms controlling this transport. Here, we show a role for phosphofurin acidic cluster sorting protein 1 (PACS‐1) in the ciliary trafficking of the olfactory 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. Sequence analysis reveals that CNGB1b contains two putative PACS‐1 binding sites, while in vitro kinase reactions confirm that CNGB1b is a CK2 substrate. Additionally, we show that PACS‐1 is expressed in OSNs and interact in complex with the CNG channel. In a model system, we demonstrate that alterations in PACS‐1 function results in deficits in CNG channel ciliary trafficking. Importantly, inhibition of CK2 in native OSNs causes a loss of CNG channel from cilia and subsequent olfactory dysfunction. These results provide a mechanism for the subunit‐dependent ciliary trafficking of the CNG channel and provide further insight into the mechanisms of ciliary transport. This work supported by NIH grants DC009606 (JRM), DK37274, AI49793 (GT), GM007767, DC00011, and DC009524 (PMJ).