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Ciliary Signaling Systems in Tissue Repair and Wound Healing
Author(s) -
Schneider Linda,
Christensen Soeren T.,
Cammer Michael,
Goldwasser Bernard,
Guerra Charles,
Schwab Albrecht,
Satir Peter
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a234-a
Subject(s) - cilium , microbiology and biotechnology , wound healing , cell migration , intraflagellar transport , platelet derived growth factor receptor , biology , ciliogenesis , microtubule , chemistry , cell , receptor , growth factor , immunology , biochemistry , flagellum , gene
Quiescent cultures of wt mouse embryonic fibroblasts (MEFs) grow a primary cilium, which is absent from Tg737 orpk MEFs, where polaris, the IFT 88 ortholog, necessary for ciliogenesis is missing. In wt MEFs but not in Tg737 orpk MEFs, PDGFRα is upregulated and translocated to the primary cilium for signaling (Schneider et al., 2005). When receptor ligand PDGF‐AA is added to wt MEFs, the ciliary homodimeric receptor PDGFRα α becomes tyrosine phosphorylated, which activates the Mek1/2‐Erk1/2 and PI3K‐Akt pathways in the cilium and at the ciliary base, controlling cell cycle entry. This activation pathway is inhibited in Tg737 orpk MEFs with no primary cilia. To analyze the role of primary cilia in tissue remodeling, we performed wound healing assays. When a scratch is made across the confluent cultures, the wt MEFs respond by cell migration and division. In the cells immediately adjacent to the wound, the primary cilia become aligned in the direction of cell migration. PDGF‐AA incubation increases the migration speed and the translocation directionality, while Tg737 orpk MEFs have decreased translocation directionality. Further, micro pipette assays demonstrate that chemotaxis towards gradients of PDGF‐AA is blocked in Tg737 orpk MEFs. This suggests that the primary cilium acts as a cellular GPS and that signaling through the cilium could play a critical role in determining the direction of cell migration in tissue repair.