A NIMA-related kinase, Fa2p, localizes to a novel site in the proximal cilia of Chlamydomonas and mouse kidney cells.
Polycystic kidney disease and related syndromes involve dysregulation of cell proliferation in conjunction with ciliary defects. The relationship between cilia and cell cycle is enigmatic, but it may involve regulation by the NIMA-family of kinases (Neks). We previously showed that the Nek Fa2p is important for ciliary function and cell cycle in Chlamydomonas. We now show that Fa2p localizes to an important regulatory site at the proximal end of cilia in both Chlamydomonas and a mouse kidney cell line. Fa2p also is associated with the proximal end of centrioles. Its localization is dynamic during the cell cycle, following a similar pattern in both cell types. The cell cycle function of Fa2p is kinase independent, whereas its ciliary function is kinase dependent. Mice with mutations in Nek1 or Nek8 have cystic kidneys; therefore, our discovery that a member of this phylogenetic group of Nek proteins is localized to the same sites in Chlamydomonas and kidney epithelial cells suggests that Neks play conserved roles in the coordination of cilia and cell cycle progression.
Mahjoub
Moe R
MR
Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, British Columbia, V5A 1S6, Canada.
Qasim Rasi
M
M
Quarmby
Lynne M
LM
D000818:Animals; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000502:physiology*; D002460:Cell Line; D002502:Centrioles / Q000378:metabolism / Q000648:ultrastructure; D002696:Chlamydomonas / Q000378:metabolism*; D002923:Cilia / Q000378:metabolism*; D018076:DNA, Complementary / Q000378:metabolism; D000939:Epitopes / Q000737:chemistry; D019084:Fluorescent Antibody Technique, Indirect; D049452:Green Fluorescent Proteins / Q000378:metabolism; D015151:Immunoblotting; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008938:Mitosis; D009154:Mutation; D000072380:NIMA-Related Kinase 1; D000072379:NIMA-Related Kinases; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis* / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D017434:Protein Structure, Tertiary; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D015398:Signal Transduction; D013347:Subcellular Fractions / Q000378:metabolism; D013997:Time Factors
D018797:Cell Cycle Proteins; D018076:DNA, Complementary; D000939:Epitopes; D049452:Green Fluorescent Proteins; D011494:Protein Kinases; D011505:Protein-Tyrosine Kinases; D000072380:NIMA-Related Kinase 1; D000072379:NIMA-Related Kinases; C000606920:Nek1 protein, mouse; C499219:Nek8 protein, mouse; D017346:Protein Serine-Threonine Kinases