Abstract
Primary cilia detect extracellular cues and transduce these signals into cells to regulate proliferation, migration, and differentiation. Here, the function of primary cilia as signaling hubs of growth factors and morphogens is in focus. First, the molecular mechanisms regulating the assembly and disassembly of primary cilia are described. Then, the role of primary cilia in mediating growth factor and morphogen signaling to maintain human health and the potential mechanisms by which defects in these pathways contribute to human diseases, such as ciliopathy, obesity, and cancer are described. Furthermore, a novel signaling pathway by which certain growth factors stimulate cell proliferation through suppression of ciliogenesis is also described, suggesting novel therapeutic targets in cancer.
Highlights
Primary cilia detect extracellular cues and transduce these signals into cells to regulate proliferation, migration, and differentiation
Centrosomal protein 83 (CEP83), which is localized at the distal appendage of the mother centriole, plays important roles in centriole-to-membrane docking[47] and the recruitment of intraflagellar transport 20 (IFT20) protein, which is mandatory for axoneme formation,[48] to the basal body.[49]
Using global screenings of DUBs and their subsequent characterization, we revealed that ubiquitinspecific peptidase 8 (USP8) could deubiquitinate and stabilize trichoplein and that the DUB activity of USP8 was regulated by EGFR tyrosine kinase through phosphorylation of tyrosine residues at 717 and 810 of USP8.[26]. Other receptor tyrosine kinase (RTK), including
Summary
Primary cilia have three compartments, the basal body, the transition zone, and the axoneme.[1,2,3,4,5,6,7] The basal body is. The axoneme consists of nine circularly arranged microtubule doublets and forms a projection extending from the basal body. The transition zone is a short (0.5 μm) area located above the basal body, characterized by Y-shaped connectors between the microtubule doublets and primary cilia membrane. In 1979, Tucker et al found that primary cilia were assembled when cultured mouse 3T3 fibroblasts exited the cell cycle under serum deprivation (i.e., G0 phase).[36,37] They reported that when the quiescent fibroblasts were stimulated with serum, primary cilia were disassembled after the serum stimulation,[36,37] which is the case for RPE1 cells (an immortalized cell line derived from human retinal pigment epithelium).[38] Deciliation after serum stimulation corresponded to the G0/G1 transition.[38] Subsequent analyses revealed that the progression to S phase after cell cycle reentry was delayed and shortened if primary cilia were longer and shorter in the G0 phase, respectively.[39,40] In contrast, forced ciliation in growing cells resulted in the arrest of cell-cycle progression.[25,26,41,42,43] These findings suggest that primary cilia themselves can work as negative regulators of the cell cycle. We describe the primary cilia dynamics with an eye on (i) the assembly of primary cilia responding to serum withdrawal, (ii) the disassembly of primary cilia responding to serum stimulation, and (iii) suppression of ciliogenesis in the presence of serum (growth factors)
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