論文

査読有り
2001年8月

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

NATURE
  • Y Fukui
  • ,
  • O Hashimoto
  • ,
  • T Sanui
  • ,
  • T Oono
  • ,
  • H Koga
  • ,
  • M Abe
  • ,
  • A Inayoshi
  • ,
  • M Noda
  • ,
  • M Oike
  • ,
  • T Shirai
  • ,
  • T Sasazuki

412
6849
開始ページ
826
終了ページ
831
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1038/35090591
出版者・発行元
MACMILLAN PUBLISHERS LTD

Cell migration is a fundamental biological process involving membrane polarization and cytoskeletal dynamics(1), both of which are regulated by Rho family GTPases(2-5). Among these molecules, Rac is crucial for generating the actin-rich lamellipodial protrusion, a principal part of the driving force for movement(3,6). 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 Rac(7-12). Although genetic analysis has shown that CED-5 and Myoblast City are crucial for migration of particular types of cells(8,9,12), physiological relevance of the CDM family proteins in mammals remains unknown. Here we show that DOCK2, a haematopoietic cell-specific CDM family protein(13), is indispensable for lymphocyte chemotaxis. DOCK2-dercient 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.

Web of Science ® 被引用回数 : 329

リンク情報
DOI
https://doi.org/10.1038/35090591
Scopus
https://www.scopus.com/record/display.uri?eid=2-s2.0-17944375813&origin=inward
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000170577200039&DestApp=WOS_CPL
URL
http://www.scopus.com/inward/record.url?eid=2-s2.0-17944375813&partnerID=MN8TOARS
URL
http://orcid.org/0000-0003-2335-8745

エクスポート
BibTeX RIS