Phosphorylation by casein kinase 2 induces PACS-1 binding of nephrocystin and targeting to cilia
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Phosphorylation by casein kinase 2 induces PACS-1 binding of nephrocystin and targeting to cilia. / Schermer, Bernhard; Höpker, Katja; Omran, Heymut; Ghenoiu, Cristina; Fliegauf, Manfred; Fekete, Andrea; Horvath, Judit; Köttgen, Michael; Hackl, Matthias; Zschiedrich, Stefan; Huber, Tobias B; Kramer-Zucker, Albrecht; Zentgraf, Hanswalter; Blaukat, Andree; Walz, Gerd; Benzing, Thomas.
In: EMBO J, Vol. 24, No. 24, 21.12.2005, p. 4415-24.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Phosphorylation by casein kinase 2 induces PACS-1 binding of nephrocystin and targeting to cilia
AU - Schermer, Bernhard
AU - Höpker, Katja
AU - Omran, Heymut
AU - Ghenoiu, Cristina
AU - Fliegauf, Manfred
AU - Fekete, Andrea
AU - Horvath, Judit
AU - Köttgen, Michael
AU - Hackl, Matthias
AU - Zschiedrich, Stefan
AU - Huber, Tobias B
AU - Kramer-Zucker, Albrecht
AU - Zentgraf, Hanswalter
AU - Blaukat, Andree
AU - Walz, Gerd
AU - Benzing, Thomas
PY - 2005/12/21
Y1 - 2005/12/21
N2 - 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.
AB - 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.
KW - Adaptor Proteins, Signal Transducing
KW - Amino Acid Sequence
KW - Animals
KW - Antibodies, Monoclonal
KW - Carrier Proteins
KW - Casein Kinase II
KW - Cell Line
KW - Cell Nucleus
KW - Cilia
KW - Epithelial Cells
KW - Epithelium
KW - Female
KW - Humans
KW - Immunoprecipitation
KW - Membrane Proteins
KW - Mice
KW - Mice, Inbred BALB C
KW - Microscopy, Fluorescence
KW - Molecular Sequence Data
KW - Phosphorylation
KW - Protein Binding
KW - Protein Structure, Tertiary
KW - Proteins
KW - Serine
KW - Time Factors
KW - Trachea
KW - Transfection
KW - Vesicular Transport Proteins
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
U2 - 10.1038/sj.emboj.7600885
DO - 10.1038/sj.emboj.7600885
M3 - SCORING: Journal article
C2 - 16308564
VL - 24
SP - 4415
EP - 4424
JO - EMBO J
JF - EMBO J
SN - 0261-4189
IS - 24
ER -