Directional Cell Migration and Chemotaxis in Wound Healing Response to PDGF-AA are Coordinated by the Primary Cilium in Fibroblasts

作者：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 Soren T^*

来源：Cellular Physiology and Biochemistry, 2010, 25(2-3): 279-292.

DOI：10.1159/000276562

• Fibroblasts
• Cell migration
• Primary cilia
• Wound healing
• PDGFR alpha
• PDGF-AA

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 PDGFR alpha 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 PDGFR alpha signaling to monitor directional movement during wound healing.

• 出版日期2010