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, Takehiko Sasazuki

Research output: Contribution to journalArticle

336 Citations (Scopus)

Abstract

Cell migration is a fundamental biological process involving membrane polarization and cytoskeletal dynamics, both of which are regulated by Rho family GTPases. Among these molecules, Rac is crucial for generating the actin-rich lamellipodial protrusion, a principal part of the driving force for movement. 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 Rac. Although genetic analysis has shown that CED-5 and Myoblast City are crucial for migration of particular types of cells, physiological relevance of the CDM family proteins in mammals remains unknown. Here we show that DOCK2, a haematopoietic cell-specific CDM family protein, 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 poly- merization were almost totally abolished. Thus, in lymphocyte migration DOCK2 functions as a central regulator that mediates cytoskeletal reorganization through Rac activation.

Original languageEnglish
Pages (from-to)826-831
Number of pages6
JournalNature
Volume412
Issue number6849
DOIs
Publication statusPublished - Aug 23 2001

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All Science Journal Classification (ASJC) codes

  • General

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