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  Cdc42-dependent leading edge coordination is essential for interstitial dendritic cell migration

Lämmermann, T., Renkawitz, J., Wu, X., Hirsch, K., Brakebusch, C., & Sixt, M. (2009). Cdc42-dependent leading edge coordination is essential for interstitial dendritic cell migration. Blood, 113, 5703-5710. doi:10.1182/blood-2008-11-191882.

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Lämmermann, Tim1, Author           
Renkawitz, Jörg2, Author
Wu, Xunwei2, Author
Hirsch, Karin2, Author
Brakebusch, Cord2, Author
Sixt, Michael2, Author
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1Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, ou_1565141              
2External Organizations, ou_persistent22              

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 Abstract: 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.

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Language(s): eng - English
 Dates: 2009-06-04
 Publication Status: Issued
 Pages: -
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 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1182/blood-2008-11-191882
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Title: Blood
  Other : Blood
Source Genre: Journal
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Publ. Info: Philadelphia, Pa. : W.B. Saunders
Pages: - Volume / Issue: 113 Sequence Number: - Start / End Page: 5703 - 5710 Identifier: ISSN: 0006-4971
CoNE: https://pure.mpg.de/cone/journals/resource/954925385125