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 journalArticle

389 Citations (Scopus)

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

Fingerprint

Platelet-Derived Growth Factor Receptors
Cilia
cilia
Fibroblasts
fibroblasts
Tissue homeostasis
Chemical activation
Ligands
homeostasis
Homeostasis
Growth
Pathology
Cell membranes
Basal Bodies
Ion Channels
Cell culture
Polycystic Kidney Diseases
mutants
Primary Cell Culture
Hedgehogs

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)

Cite this

Schneider, L., Clement, C. A., Teilmann, S. C., Pazour, G. J., Hoffmann, E. K., Satir, P., & Christensen, S. T. (2005). PDGFRαα signaling is regulated through the primary cilium in fibroblasts. Current Biology, 15(20), 1861-1866. https://doi.org/10.1016/j.cub.2005.09.012

PDGFRαα signaling is regulated through the primary cilium in fibroblasts. / Schneider, Linda; Clement, Christian A.; Teilmann, Stefan C.; Pazour, Gregory J.; Hoffmann, Else K.; Satir, Peter; Christensen, Søren T.

In: Current Biology, Vol. 15, No. 20, 25.10.2005, p. 1861-1866.

Research output: Contribution to journalArticle

Schneider, L, Clement, CA, Teilmann, SC, Pazour, GJ, Hoffmann, EK, Satir, P & Christensen, ST 2005, 'PDGFRαα signaling is regulated through the primary cilium in fibroblasts', Current Biology, vol. 15, no. 20, pp. 1861-1866. https://doi.org/10.1016/j.cub.2005.09.012
Schneider L, Clement CA, Teilmann SC, Pazour GJ, Hoffmann EK, Satir P et al. PDGFRαα signaling is regulated through the primary cilium in fibroblasts. Current Biology. 2005 Oct 25;15(20):1861-1866. https://doi.org/10.1016/j.cub.2005.09.012
Schneider, Linda ; Clement, Christian A. ; Teilmann, Stefan C. ; Pazour, Gregory J. ; Hoffmann, Else K. ; Satir, Peter ; Christensen, Søren T. / PDGFRαα signaling is regulated through the primary cilium in fibroblasts. In: Current Biology. 2005 ; Vol. 15, No. 20. pp. 1861-1866.
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