The role of the cilium in normal and abnormal cell cycles: emphasis on renal cystic pathologies.
The primary cilium protrudes from the cell surface and acts as a sensor for chemical and mechanical growth cues, with receptors for a number of growth factors (PDGFα, Hedgehog, Wnt, Notch) concentrated within the ciliary membrane. In normal tissues, the cilium assembles after cells exit mitosis and is resorbed as part of cell cycle re-entry. Although regulation of the cilium by cell cycle transitions has been appreciated for over 100 years, only recently have data emerged to indicate the cilium also exerts influence on the cell cycle. The resorption/protrusion cycle, regulated by proteins including Aurora-A, VHL, and GSK-3β, influences cell responsiveness to growth cues involving cilia-linked receptors; further, resorption liberates the ciliary basal body to differentiate into the centrosome, which performs discrete functions in S-, G2-, and M-phase. Besides these roles, the cilium provides a positional cue that regulates polarity of cell division, and thus directs cells towards fates of differentiation versus proliferation. In this review, we summarize the specific mechanisms mediating the cilia-cell cycle dialog. We then emphasize the examples of polycystic kidney disease (PKD), nephronopthisis (NPHP), and VHL-linked renal cysts as cases in which defects of ciliary function influence disease pathology, and may also condition response to treatment.
Protein Science Laboratory of the Ministry of Education, School of Life Sciences, Tsinghua University, Beijing, 100084, China. panjunmin@tsinghua.edu.cn
Junmin
J
Pan
Tamina
T
Seeger-Nukpezah
Erica A
EA
Golemis
D002453:Cell Cycle / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000378:metabolism / Q000502:physiology; D016764:Cell Polarity; D049109:Cell Proliferation; D002923:Cilia / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D002986:Clinical Trials as Topic; D007674:Kidney Diseases / Q000188:drug therapy / Q000473:pathology*; D052177:Kidney Diseases, Cystic / Q000188:drug therapy / Q000473:pathology; D040542:Mechanotransduction, Cellular; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D015398:Signal Transduction; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D006623:von Hippel-Lindau Disease / Q000188:drug therapy / Q000473:pathology
D018797:Cell Cycle Proteins; D010982:Platelet-Derived Growth Factor; D051794:Von Hippel-Lindau Tumor Suppressor Protein