Different PDGF receptor dimers drive distinct migration modes of the mouse skin fibroblast

Kohta Yamada, Takeru Hamashima, Yoko Ishii, Seiji Yamamoto, Noriko Okuno, Naofumi Yoshida, Moe Yamada, Ting Ting Huang, Norifumi Shioda, Kei Tomihara, Toshihiko Fujimori, Hisashi Mori, Kohji Fukunaga, Makoto Noguchi, Masakiyo Sasahara

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)


Background/Aims: The migration of mesenchymal cells is a fundamental cellular process that has been implicated in many pathophysiological conditions and is induced by chemoattractants such as platelet-derived growth factors (PDGFs). However, the regulatory mechanisms shaping this migration remain to be elucidated. Methods: Here, we prepared mouse skin fibroblasts inactivated for different PDGF receptor genes and systematically measured their chemotactic responses within a gradient of different chemoattractants. Results: We found that PDGFRαβ and PDGFRββ dimers were strong inducers of random and directionally-persistent migration, respectively, that was sustained for up to 24 h. MAPK and PI3K were necessary to mediate random and directional migration, respectively. Directional migration was accompanied by abundant ventral stress fiber formation and consistent cell shape with less frequent formation of branch-like processes. Conclusion: This is the first systematic study that characterized the chemotaxis mediated by three-different types of PDGFR dimers in mesenchymal cell migration. Our data demonstrate that PDGFR dimer formation is the critical step to determine the specific mode of fibroblast chemotaxis, while the accompanying cytoskeletal remodeling might contribute to migration persistence.

Original languageEnglish
Pages (from-to)1461-1479
Number of pages19
JournalCellular Physiology and Biochemistry
Issue number3
Publication statusPublished - 2018 Dec 1


  • Chemotaxis
  • Cytoskeleton
  • Directionality
  • Fibroblast
  • Platelet derived growth factor
  • Receptor
  • Signaling

ASJC Scopus subject areas

  • Physiology


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