NIMA-related kinases defective in murine models of polycystic kidney diseases localize to primary cilia and centrosomes.
A key feature of the polycystic kidney diseases is aberrant cell proliferation, a consequence of dysfunctional ciliary signaling. The NIMA-related kinases (Nek) Nek1 and Nek8 carry the causal mutations of two of the eight established mouse models of polycystic kidneys. Nek proteins have roles in cell cycle and may contribute to coordinate regulation of cilia and cell-cycle progression. Herein is reported that in a mouse kidney epithelial cell line, mNek1 localizes to centrosomes in interphase and remains associated with the mitotic spindle pole during mitosis. In contrast, mNek8 localizes to the proximal region of the primary cilium and is not observed in dividing cells. Knockdown of mNek8 by siRNA does not affect ciliary assembly. Taken together with the phenotypes of the mutant mice, these data suggest that mNek1 and mNek8 provide links between cilia, centrosomes, and cell-cycle regulation.
Mahjoub
Moe R
MR
Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, British Columbia, Canada.
Trapp
Melissa L
ML
Quarmby
Lynne M
LM
D000818:Animals; D015153:Blotting, Western; D002453:Cell Cycle / Q000502:physiology; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D018385:Centrosome / Q000201:enzymology* / Q000502:physiology; D002923:Cilia / Q000502:physiology; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000166:cytology / Q000201:enzymology; D005455:Fluorescent Antibody Technique; D007668:Kidney / Q000166:cytology; D051379:Mice; D008938:Mitosis / Q000502:physiology*; D000072380:NIMA-Related Kinase 1; D007690:Polycystic Kidney Diseases / Q000201:enzymology* / Q000503:physiopathology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000032:analysis; D012680:Sensitivity and Specificity; D015398:Signal Transduction
D018797:Cell Cycle Proteins; D034741:RNA, Small Interfering; D000072380:NIMA-Related Kinase 1; C000606920:Nek1 protein, mouse; D017346:Protein Serine-Threonine Kinases