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PMID: 20110689 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Directional cell migration and chemotaxis in wound healing response to PDGF-AA are coordinated by the primary cilium in fibroblasts.

Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology ·Vol. 25 ·No. 2-3 ·2010-00-00 ·Pages 279-92

Schneider L, Cammer M, Lehman J, Nielsen SK, Guerra CF, Veland IR, Stock C, Hoffmann EK, Yoder BK, Schwab A, Satir P, Christensen ST

Abstract

Cell motility and migration play pivotal roles in numerous physiological and pathophysiological processes including development and tissue repair. Cell migration is regulated through external stimuli such as platelet-derived growth factor-AA (PDGF-AA), a key regulator in directional cell migration during embryonic development and a chemoattractant during postnatal migratory responses including wound healing. We previously showed that PDGFRalpha signaling is coordinated by the primary cilium in quiescent cells. However, little is known about the function of the primary cilium in cell migration. Here we used micropipette analysis to show that a normal chemosensory response to PDGF-AA in fibroblasts requires the primary cilium. In vitro and in vivo wound healing assays revealed that in ORPK mouse (IFT88(Tg737Rpw)) fibroblasts, where ciliary assembly is defective, chemotaxis towards PDGF-AA is absent, leading to unregulated high speed and uncontrolled directional cell displacement during wound closure, with subsequent defects in wound healing. These data suggest that in coordination with cytoskeletal reorganization, the fibroblast primary cilium functions via ciliary PDGFRalpha signaling to monitor directional movement during wound healing.

MeSH Terms
Animals Cell Movement Cells, Cultured Chemotaxis/physiology Cilia/physiology Fibroblasts/metabolism Mice NIH 3T3 Cells Platelet-Derived Growth Factor/metabolism Receptor, Platelet-Derived Growth Factor alpha/metabolism Signal Transduction Tumor Suppressor Proteins/deficiency,genetics,metabolism Wound Healing/physiology
Chemicals
Platelet-Derived Growth Factor Tg737Rpw protein, mouse Tumor Suppressor Proteins platelet-derived growth factor A Receptor, Platelet-Derived Growth Factor alpha
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
Schneider Linda
Department of Biology, Section of Cell and Developmental Biology, The August Krogh Building, University of Copenhagen, DK-2100 Copenhagen OE, Denmark.
Cammer Michael
Lehman Jonathan
Nielsen Sonja K
Guerra Charles F
Veland Iben R
Stock Christian
Hoffmann Else K
Yoder Bradley K
Schwab Albrecht
Satir Peter
Christensen Søren T
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Article Info
Journal
Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology
Abbr.
Cell Physiol Biochem
ISSN
1421-9778
DOI
10.1159/000276562
Published
2010-00-00
Epub
2010-00-12
Pages
279-92
Language
English
Region
Germany
NLM ID
9113221
PMCID
PMC2924811
Subset
IM
Grants
NIDDK NIH HHS · P30 DK074038 · United States
NIAMS NIH HHS · R01 AR052792 · United States
NIAMS NIH HHS · P30 AR050948-07 · United States
NIAMS NIH HHS · P30 AR050948-03 · United States
NIAMS NIH HHS · P30 AR050948 · United States
NIAMS NIH HHS · R01 AR052792-04 · United States
External Links
PubMed source DOI: 10.1159/000276562 PMC Full Text View journal details
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