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

Yoshinori Fukui, Osamu Hashimoto, Terukazu Sanui, Takamasa Oono, Hironori Koga, Masaaki Abe, Ayumi Inayoshi, Mayuko Noda, Masahiro Oike, Toshikazu Shirai () and Takehiko Sasazuki
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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
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

Nature, 2001, vol. 412, issue 6849, 826-831

Abstract: 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.

Date: 2001
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DOI: 10.1038/35090591

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