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Haematopoietic cell-specific CDM family protein DOCK2 is essential for lymphocyte migration

Author

Listed:
  • Yoshinori Fukui

    (Medical Institute of Bioregulation, Kyushu University, and CREST, Japan Science and Technology Corporation)

  • Osamu Hashimoto

    (Medical Institute of Bioregulation, Kyushu University, and CREST, Japan Science and Technology Corporation
    Research Center for Innovative Cancer Therapy, Kurume University School of Medicine)

  • Terukazu Sanui

    (Medical Institute of Bioregulation, Kyushu University, and CREST, Japan Science and Technology Corporation)

  • Takamasa Oono

    (Medical Institute of Bioregulation, Kyushu University, and CREST, Japan Science and Technology Corporation)

  • Hironori Koga

    (Research Center for Innovative Cancer Therapy, Kurume University School of Medicine)

  • Masaaki Abe

    (Juntendo University School of Medicine)

  • Ayumi Inayoshi

    (Medical Institute of Bioregulation, Kyushu University, and CREST, Japan Science and Technology Corporation)

  • Mayuko Noda

    (Medical Institute of Bioregulation, Kyushu University, and CREST, Japan Science and Technology Corporation)

  • Masahiro Oike

    (Graduate School of Medical Sciences, Kyushu University)

  • Toshikazu Shirai

    (Juntendo University School of Medicine)

  • Takehiko Sasazuki

    (Medical Institute of Bioregulation, Kyushu University, and CREST, Japan Science and Technology Corporation
    International Medical Center of Japan)

Abstract

Cell migration is a fundamental biological process involving membrane polarization and cytoskeletal dynamics1, both of which are regulated by Rho family GTPases2,3,4,5. Among these molecules, Rac is crucial for generating the actin-rich lamellipodial protrusion, a principal part of the driving force for movement3,6. The CDM family proteins, Caenorhabditis elegans CED-5, human DOCK180 and Drosophila melanogaster Myoblast City (MBC), are implicated to mediate membrane extension by functioning upstream of Rac7,8,9,10,11,12. Although genetic analysis has shown that CED-5 and Myoblast City are crucial for migration of particular types of cells8,9,12, physiological relevance of the CDM family proteins in mammals remains unknown. Here we show that DOCK2, a haematopoietic cell-specific CDM family protein13, is indispensable for lymphocyte chemotaxis. DOCK2-deficient mice (DOCK2-/-) exhibited migration defects of T and B lymphocytes, but not of monocytes, in response to chemokines, resulting in several abnormalities including T lymphocytopenia, atrophy of lymphoid follicles and loss of marginal-zone B cells. In DOCK2-/- lymphocytes, chemokine-induced Rac activation and actin polymerization were almost totally abolished. Thus, in lymphocyte migration DOCK2 functions as a central regulator that mediates cytoskeletal reorganization through Rac activation.

Suggested Citation

  • Yoshinori Fukui & Osamu Hashimoto & Terukazu Sanui & Takamasa Oono & Hironori Koga & Masaaki Abe & Ayumi Inayoshi & Mayuko Noda & Masahiro Oike & Toshikazu Shirai & Takehiko Sasazuki, 2001. "Haematopoietic cell-specific CDM family protein DOCK2 is essential for lymphocyte migration," Nature, Nature, vol. 412(6849), pages 826-831, August.
    • Handle: RePEc:nat:nature:v:412:y:2001:i:6849:d:10.1038_35090591
    DOI: 10.1038/35090591
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    Cited by:

    1. Wellington K. Ayensu & Paul B. Tchounwou, 2006. "Microarray Analysis of Mercury-Induced Changes in Gene Expression in Human Liver Carcinoma (HepG2) Cells: Importance in Immune Responses," IJERPH, MDPI, vol. 3(2), pages 1-33, June.

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