PACS-1 Mediates Phosphorylation-Dependent Ciliary Trafficking of the Cyclic-Nucleotide-Gated Channel in Olfactory Sensory Neurons
Year: 2009
Type: article
Abstract: 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.
Source: Journal of Neuroscience
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: hybrid
Awards: G1126590241, Role of PACS proteins in polycystin-2 trafficking and ADPKD, G3484108078, Olfactory Signaling, Cilia, and Sensory Disorders, Interdepartmental Training in Pharmacological Sciences, Role of PACS-1 in HIV-1 Immunoevasion, Mechanisms of Ciliary Trafficking of the Olfactory CNG Channel, G4792905505, G526527174, G8456489402, G8852040989, G9000154320, Sensory Mechanisms and Disorders
OpenAlex ID: W1964410667