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Blood, 4 June 2009, Vol. 113, No. 23, pp. 5703-5710. Prepublished online as a Blood First Edition Paper on February 3, 2009; DOI 10.1182/blood-2008-11-191882. This Article Full Text Full Text (PDF) Supplemental Videos All Versions of this Article: blood-2008-11-191882v1 113/23/5703    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Lämmermann, T. Articles by Sixt, M. Search for Related Content PubMed PubMed Citation Articles by Lämmermann, T. Articles by Sixt, M. Related Collections Plenary Papers Phagocytes, Granulocytes, and Myelopoiesis Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  PLENARY PAPER Cdc42-dependent leading edge coordination is essential for interstitial dendritic cell migration Tim Lämmermann1, Jörg Renkawitz1, Xunwei Wu2, Karin Hirsch1, Cord Brakebusch2, and Michael Sixt1 1 Hofschneider Group Leukocyte Migration, Department of Molecular Medicine, Max Planck Institute of Biochemistry, Martinsried, Germany; and 2 Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark Mature dendritic cells (DCs) moving from the skin to the lymph node are a prototypic example of rapidly migrating amoeboid leukocytes. Interstitial DC migration is directionally guided by chemokines, but independent of specific adhesive interactions with the tissue as well as pericellular proteolysis. Instead, the protrusive flow of the actin cytoskeleton directly drives a basal mode of locomotion that is occasionally supported by actomyosin contractions at the trailing edge to propel the cell's rigid nucleus. We here delete the small GTPase Cdc42 in DCs and find that actin flow and actomyosin contraction are still initiated in response to chemotactic cues. Accordingly, the cells are able to polarize and form protrusions. However, in the absence of Cdc42 the protrusions are temporally and spatially dysregulated, which leads to impaired leading edge coordination. Although this defect still allows the cells to move on 2-dimensional surfaces, their in vivo motility is completely abrogated. We show that this difference is entirely caused by the geometric complexity of the environment, as multiple competing protrusions lead to instantaneous entanglement within 3-dimensional extracellular matrix scaffolds. This demonstrates that the decisive factor for migrating DCs is not specific interaction with the extracellular environment, but adequate coordination of cytoskeletal flow. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Close encounters of the 3D kind Jens V. Stein Blood 2009 113: 5698-5699. [Full Text] [PDF] This article has been cited by other articles: J. V. Stein Close encounters of the 3D kind Blood, June 4, 2009; 113(23): 5698 - 5699. [Full Text] [PDF]

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