Abstract

Recent findings show that cilia are sensory organelles that display specific receptors and ion channels, which transmit signals from the extracellular environment via the cilium to the cell to control tissue homeostasis and function [1Rosenbaum J.L. Witman G.B. Intraflagellar transport.Nat. Rev. Mol. Cell Biol. 2002; 3: 813-825Crossref PubMed Scopus (1203) Google Scholar, 2Pazour G.J. Witman G.B. The vertebrate primary cilium is a sensory organelle.Curr. Opin. Cell Biol. 2003; 15: 105-110Crossref PubMed Scopus (379) Google Scholar, 3Nauli S.M. Zhou J. Polycystins and mechanosensation in renal and nodal cilia.Bioessays. 2004; 26: 844-856Crossref PubMed Scopus (173) Google Scholar, 4Praetorius H.A. Spring K.R. Physiological view of the primary cilium.Annu. Rev. Physiol. 2005; 67: 515-529Crossref PubMed Scopus (229) Google Scholar, 5Teilmann S.C. Christensen S.T. Ciliary localization of the angiopoietin receptors Tie-1 and Tie-2 in the female reproductive organs.Cell Biol. Int. 2005; 29: 340-346Crossref PubMed Scopus (45) Google Scholar, 6Quarmby L.M. Parker J.D.K. Cilia and the cell cycle?.J. Cell Biol. 2005; 169: 707-710Crossref PubMed Scopus (193) Google Scholar]. Agenesis of primary cilia or mislocation of ciliary signal components affects human pathologies, such as polycystic kidney disease [7Pazour G.J. San Agustin J.T. Follit J.A. Rosenbaum J.L. Witman G.B. Polycystin-2 localizes to kidney cilia and the ciliary level is elevated in orpk mice with polycystic kidney disease.Curr. Biol. 2002; 12: R378-R380Abstract Full Text Full Text PDF PubMed Scopus (420) Google Scholar] and disorders associated with Bardet-Biedl syndrome [8Ou G. Blacque O.E. Snow J.J. Leroux M.R. Scholey J.M. Functional coordination of intraflagellar transport motors.Nature. 2005; 436: 583-587Crossref PubMed Scopus (302) Google Scholar]. Primary cilia are essential for hedgehog ligand-induced signaling cascade regulating growth and patterning [9Huangfu D. Anderson K.V. Cilia and Hedgehog responsiveness in the mouse.Proc. Natl. Acad. Sci. USA. 2005; 102: 11325-11330Crossref PubMed Scopus (642) Google Scholar, 10Liu A. Wang B. Niswander L.A. Mouse intraflagellar transport proteins regulate both the activator and repressor functions of Gli transcription factors.Development. 2005; 132: 3103-3111Crossref PubMed Scopus (425) Google Scholar]. Here, we show that the primary cilium in fibroblasts [11Tucker R.W. Pardee A.B. Fujiwara K. Centriole ciliation is related to quiescence and DNA synthesis in 3T3 cells.Cell. 1979; 17: 527-535Abstract Full Text PDF PubMed Scopus (249) Google Scholar] plays a critical role in growth control via platelet-derived growth factor receptor α (PDGFRα), which localizes to the primary cilium during growth arrest in NIH3T3 cells and primary cultures of mouse embryonic fibroblasts. Ligand-dependent activation of PDGFRαα is followed by activation of Akt and the Mek1/2-Erk1/2 pathways, with Mek1/2 being phosphorylated within the cilium and at the basal body. Fibroblasts derived from Tg737orpk mutants fail to form normal cilia and to upregulate the level of PDGFRα; PDGF-AA fails to activate PDGFRαα and the Mek1/2-Erk1/2 pathway. Signaling through PDGFRβ, which localizes to the plasma membrane, is maintained at comparable levels in wild-type and mutant cells. We propose that ciliary PDGFRαα signaling is linked to tissue homeostasis and to mitogenic signaling pathways.