Directional cell migration and chemotaxis in wound healing response to PDGF-AA are coordinated by the primary cilium in fibroblasts
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Directional cell migration and chemotaxis in wound healing response to PDGF-AA are coordinated by the primary cilium in fibroblasts. / Schneider, Linda; 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 Tvorup.
I: Cellular Physiology and Biochemistry, Bind 25, Nr. 2-3, 2010, s. 279-92.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Directional cell migration and chemotaxis in wound healing response to PDGF-AA are coordinated by the primary cilium in fibroblasts
AU - Schneider, Linda
AU - Cammer, Michael
AU - Lehman, Jonathan
AU - Nielsen, Sonja K
AU - Guerra, Charles F
AU - Veland, Iben R
AU - Stock, Christian
AU - Hoffmann, Else K
AU - Yoder, Bradley K
AU - Schwab, Albrecht
AU - Satir, Peter
AU - Christensen, Søren Tvorup
N1 - Key Words * Fibroblasts * Cell migration * Primary cilia * Wound healing * PDGFRa * PDGF-AA
PY - 2010
Y1 - 2010
N2 - 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.
AB - 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.
U2 - 10.1159/000276562
DO - 10.1159/000276562
M3 - Journal article
C2 - 20110689
VL - 25
SP - 279
EP - 292
JO - Cellular Physiology and Biochemistry
JF - Cellular Physiology and Biochemistry
SN - 1015-8987
IS - 2-3
ER -
ID: 17583446