TY - JOUR

T1 - PDGFRaa Signaling Is Regulated through the Primary Cilium in Fibroblasts

AU - Schneider, Linda

AU - Clement, Christian Alexandro

AU - Teilmann, S.C.

AU - Pazour, G.

AU - Hofman, Kay

AU - Satir, P.

AU - Christensen, Søren T.

PY - 2005

Y1 - 2005

N2 - 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 [[1], [2], [3], [4], [5] and [6]]. Agenesis of primary cilia or mislocation of ciliary signal components affects human pathologies, such as polycystic kidney disease [7] and disorders associated with Bardet-Biedl syndrome [8]. Primary cilia are essential for hedgehog ligand-induced signaling cascade regulating growth and patterning [[9] and [10]]. Here, we show that the primary cilium in fibroblasts [11] plays a critical role in growth control via platelet-derived growth factor receptor a (PDGFRa), which localizes to the primary cilium during growth arrest in NIH3T3 cells and primary cultures of mouse embryonic fibroblasts. Ligand-dependent activation of PDGFRaa 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 PDGFRa; PDGF-AA fails to activate PDGFRaa and the Mek1/2-Erk1/2 pathway. Signaling through PDGFRß, which localizes to the plasma membrane, is maintained at comparable levels in wild-type and mutant cells. We propose that ciliary PDGFRaa signaling is linked to tissue homeostasis and to mitogenic signaling pathways.

AB - 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 [[1], [2], [3], [4], [5] and [6]]. Agenesis of primary cilia or mislocation of ciliary signal components affects human pathologies, such as polycystic kidney disease [7] and disorders associated with Bardet-Biedl syndrome [8]. Primary cilia are essential for hedgehog ligand-induced signaling cascade regulating growth and patterning [[9] and [10]]. Here, we show that the primary cilium in fibroblasts [11] plays a critical role in growth control via platelet-derived growth factor receptor a (PDGFRa), which localizes to the primary cilium during growth arrest in NIH3T3 cells and primary cultures of mouse embryonic fibroblasts. Ligand-dependent activation of PDGFRaa 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 PDGFRa; PDGF-AA fails to activate PDGFRaa and the Mek1/2-Erk1/2 pathway. Signaling through PDGFRß, which localizes to the plasma membrane, is maintained at comparable levels in wild-type and mutant cells. We propose that ciliary PDGFRaa signaling is linked to tissue homeostasis and to mitogenic signaling pathways.

U2 - 10.1016/j.cub.2005.09.012

DO - 10.1016/j.cub.2005.09.012

M3 - Journal article

VL - 15

SP - 1861

EP - 1866

JO - Current Biology

JF - Current Biology

SN - 0960-9822

IS - 20

ER -