The primary cilium is a sensory organelle that regulates growth control and tissue homeostasis

TY - JOUR

T1 - The primary cilium is a sensory organelle that regulates growth control and tissue homeostasis

AU - Christensen, Søren Tvorup

AU - Schneider, Linda

AU - Clement, Christian Alexandro

AU - Pazour, G.

AU - Hoffmann, E. K.

AU - Satir, P.

PY - 2006

Y1 - 2006

N2 - The growth-arrest specific receptor tyrosine kinase, PDGFRa, is up-regulated and targeted to the primary cilium during growth arrest in NIH3T3 cells and primary cultures of mouse embryonic fibroblasts (MEFs), and PDGF-AA-stimulated fibroblast cycle entrance is regulated through activation of ciliary PDGFRaa followed by activation of the mitogenic Mek1/2-Erk1/2 pathway, which also operates in the cilium. Quiescent MEFs derived from Tg737orpk mutants fail to form normal cilia and to activate Mek1/2-Erk1/2 and re-enter the cell cycle after stimulation with PDGF-AA [Schneider et al. (2005) Current Biology]. Prolonged growth arrest in wt cells is associated with activation of p53 and cells remain viable for at least 7 days of serum starvation. In contrast, mutant MEFs fail to activate p53 upon starvation and cells begin to die 2 days after starvation. These results indicate that the primary cilium is essential for activation of p53 to maintain cell quiescence and prevent cells from entering programmed cell death. The NIH3T3 cilium also contains taurine transporter [Christensen et al. (2005) Cell Biol. Int.] and b1 integrin, which in concert with ciliary PDGFRa in normally quiescent tissue fibroblasts might be to interact with growth factors and extracellular matrix to control cell survival and growth, and likely migration, and to continuously monitor the mechanical stress on the tissue through modulation of Ca2+-dependent signaling in the primary cilium.

AB - The growth-arrest specific receptor tyrosine kinase, PDGFRa, is up-regulated and targeted to the primary cilium during growth arrest in NIH3T3 cells and primary cultures of mouse embryonic fibroblasts (MEFs), and PDGF-AA-stimulated fibroblast cycle entrance is regulated through activation of ciliary PDGFRaa followed by activation of the mitogenic Mek1/2-Erk1/2 pathway, which also operates in the cilium. Quiescent MEFs derived from Tg737orpk mutants fail to form normal cilia and to activate Mek1/2-Erk1/2 and re-enter the cell cycle after stimulation with PDGF-AA [Schneider et al. (2005) Current Biology]. Prolonged growth arrest in wt cells is associated with activation of p53 and cells remain viable for at least 7 days of serum starvation. In contrast, mutant MEFs fail to activate p53 upon starvation and cells begin to die 2 days after starvation. These results indicate that the primary cilium is essential for activation of p53 to maintain cell quiescence and prevent cells from entering programmed cell death. The NIH3T3 cilium also contains taurine transporter [Christensen et al. (2005) Cell Biol. Int.] and b1 integrin, which in concert with ciliary PDGFRa in normally quiescent tissue fibroblasts might be to interact with growth factors and extracellular matrix to control cell survival and growth, and likely migration, and to continuously monitor the mechanical stress on the tissue through modulation of Ca2+-dependent signaling in the primary cilium.

M3 - Journal article

SN - 0892-6638

VL - 20

SP - A437

JO - F A S E B Journal

JF - F A S E B Journal

ER -