PDGFRαα signaling is regulated through the primary cilium in fibroblasts

Linda Schneider, Christian A. Clement, Stefan C. Teilmann, Gregory J. Pazour, Else K. Hoffmann, Peter Satir, Søren T. Christensen

Research output: Contribution to journalArticlepeer-review

410 Scopus citations

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 [1-6]. 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 [9,10]. Here, we show that the primary cilium in fibroblasts [11] 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.

Original languageEnglish (US)
Pages (from-to)1861-1866
Number of pages6
JournalCurrent Biology
Volume15
Issue number20
DOIs
StatePublished - Oct 25 2005

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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