Phosphorylation by casein kinase 2 induces PACS-1 binding of nephrocystin and targeting to cilia
Open Access
- 24 November 2005
- journal article
- Published by Springer Science and Business Media LLC in The EMBO Journal
- Vol. 24 (24), 4415-4424
- https://doi.org/10.1038/sj.emboj.7600885
Abstract
Mutations in proteins localized to cilia and basal bodies have been implicated in a growing number of human diseases. Access of these proteins to the ciliary compartment requires targeting to the base of the cilia. However, the mechanisms involved in transport of cilia proteins to this transitional zone are elusive. Here we show that nephrocystin, a ciliary protein mutated in the most prevalent form of cystic kidney disease in childhood, is expressed in respiratory epithelial cells and accumulates at the base of cilia, overlapping with markers of the basal body area and the transition zone. Nephrocystin interacts with the phosphofurin acidic cluster sorting protein (PACS)‐1. Casein kinase 2 (CK2)‐mediated phosphorylation of three critical serine residues within a cluster of acidic amino acids in nephrocystin mediates PACS‐1 binding, and is essential for colocalization of nephrocystin with PACS‐1 at the base of cilia. Inhibition of CK2 activity abrogates this interaction and results in the loss of correct nephrocystin targeting. These data suggest that CK2‐dependent transport processes represent a novel pathway of targeting proteins to the cilia.Keywords
This publication has 38 references indexed in Scilit:
- Functional characterization of the C. elegans nephrocystins NPHP-1 and NPHP-4 and their role in cilia and male sensory behaviorsExperimental Cell Research, 2005
- Mammalian GRIP domain proteins differ in their membrane binding properties and are recruited to distinct domains of the TGNJournal of Cell Science, 2004
- Cilia and Flagella RevealedCell, 2004
- A role for GRIP domain proteins and/or their ligands in structure and function of the trans Golgi networkJournal of Cell Science, 2003
- Role of PACS-1 in Trafficking of Human Cytomegalovirus Glycoprotein B and Virus ProductionJournal of Virology, 2003
- Mutations in INVS encoding inversin cause nephronophthisis type 2, linking renal cystic disease to the function of primary cilia and left-right axis determinationNature Genetics, 2003
- Intraflagellar transportNature Reviews Molecular Cell Biology, 2002
- Genetics and Pathogenesis of Polycystic Kidney DiseaseJournal of the American Society of Nephrology, 2002
- 14-3-3 Interacts with Regulator of G Protein Signaling Proteins and Modulates Their ActivityPublished by Elsevier BV ,2000
- Polarized sorting of rhodopsin on post-Golgi membranes in frog retinal photoreceptor cells.The Journal of cell biology, 1991