PMID:22701722

Citation	Seeger-Nukpezah, T, Liebau, MC, Höpker, K, Lamkemeyer, T, Benzing, T, Golemis, EA and Schermer, B (2012) The centrosomal kinase Plk1 localizes to the transition zone of primary cilia and induces phosphorylation of nephrocystin-1. PLoS ONE 7:e38838
Abstract	Polo-like kinase (Plk1) plays a central role in regulating the cell cycle. Plk1-mediated phosphorylation is essential for centrosome maturation, and for numerous mitotic events. Although Plk1 localizes to multiple subcellular sites, a major site of action is the centrosomes, which supports mitotic functions in control of bipolar spindle formation. In G0 or G1 untransformed cells, the centriolar core of the centrosome differentiates into the basal body of the primary cilium. Primary cilia are antenna-like sensory organelles dynamically regulated during the cell cycle. Whether Plk1 has a role in ciliary biology has never been studied. Nephrocystin-1 (NPHP1) is a ciliary protein; loss of NPHP1 in humans causes nephronophthisis (NPH), an autosomal-recessive cystic kidney disease. We here demonstrate that Plk1 colocalizes with nephrocystin-1 to the transition zone of primary cilia in epithelial cells. Plk1 co-immunoprecipitates with NPHP1, suggesting it is part of the nephrocystin protein complex. We identified a candidate Plk1 phosphorylation motif (D/E-X-S/T-φ-X-D/E) in nephrocystin-1, and demonstrated in vitro that Plk1 phosphorylates the nephrocystin N-terminus, which includes the specific PLK1 phosphorylation motif. Further, induced disassembly of primary cilia rapidly evoked Plk1 kinase activity, while small molecule inhibition of Plk1 activity or RNAi-mediated downregulation of Plk1 limited the first and second phase of ciliary disassembly. These data identify Plk1 as a novel transition zone signaling protein, suggest a function of Plk1 in cilia dynamics, and link Plk1 to the pathogenesis of NPH and potentially other cystic kidney diseases.
Links	PubMed PMC3372538 Online version:10.1371/journal.pone.0038838
Keywords	Adaptor Proteins, Signal Transducing/metabolism; Blotting, Western; Cell Cycle Proteins/metabolism; Centrosome/metabolism; Chromatography, Liquid; Cilia/metabolism; DNA Primers/genetics; HEK293 Cells; Humans; Immunoprecipitation; Membrane Proteins/metabolism; Microscopy, Fluorescence; Phosphorylation; Protein-Serine-Threonine Kinases/metabolism; Proto-Oncogene Proteins/metabolism; RNA Interference; RNA, Small Interfering/genetics; Tandem Mass Spectrometry
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:PLK1		GO:0006468: protein phosphorylation	ECO:0000314:		P		Figure 3 shows Plk1 directly phosphorylates NPHP1 in vitro.	complete CACAO 7977
HUMAN:PLK1		GO:0051179: localization	ECO:0000314:		P		Figure 1 shows Plk1 colocalizes with NPHP1 at the base of the cilium.	complete CACAO 8010
HUMAN:PLK1	involved_in	GO:0006468: protein phosphorylation	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete

References

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