Cdc42-dependent leading edge coordination is essential for interstitial dendritic cell migration (Plenary Paper)

Lämmermann T, Renkawitz J, Wu X, Hirsch K, Brakebusch C, Sixt MK. 2009. Cdc42-dependent leading edge coordination is essential for interstitial dendritic cell migration (Plenary Paper). Blood. 113(23), 5703–5710.

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Journal Article | Published
Author
Lämmermann, Tim; Renkawitz, JoergIST Austria ; Wu, Xunwei; Hirsch, Karin; Brakebusch, Cord; Sixt, Michael KIST Austria
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.
Publishing Year
Date Published
2009-06-04
Journal Title
Blood
Acknowledgement
We thank Sylvia Cremer for help with statistics and critical reading of the paper and Reinhard Fässler for continuous support. This work was supported by the German Research Foundation (Bonn, Germany), the Peter Hans Hofschneider Foundation for Experimental Biomedicine (Zürich, Switzerland), and the Max Planck Society (Munich, Germany).
Volume
113
Issue
23
Page
5703 - 5710
IST-REx-ID

Cite this

Lämmermann T, Renkawitz J, Wu X, Hirsch K, Brakebusch C, Sixt MK. Cdc42-dependent leading edge coordination is essential for interstitial dendritic cell migration (Plenary Paper). Blood. 2009;113(23):5703-5710. doi:10.1182/blood-2008-11-191882
Lämmermann, T., Renkawitz, J., Wu, X., Hirsch, K., Brakebusch, C., & Sixt, M. K. (2009). Cdc42-dependent leading edge coordination is essential for interstitial dendritic cell migration (Plenary Paper). Blood. American Society of Hematology. https://doi.org/10.1182/blood-2008-11-191882
Lämmermann, Tim, Jörg Renkawitz, Xunwei Wu, Karin Hirsch, Cord Brakebusch, and Michael K Sixt. “Cdc42-Dependent Leading Edge Coordination Is Essential for Interstitial Dendritic Cell Migration (Plenary Paper).” Blood. American Society of Hematology, 2009. https://doi.org/10.1182/blood-2008-11-191882.
T. Lämmermann, J. Renkawitz, X. Wu, K. Hirsch, C. Brakebusch, and M. K. Sixt, “Cdc42-dependent leading edge coordination is essential for interstitial dendritic cell migration (Plenary Paper),” Blood, vol. 113, no. 23. American Society of Hematology, pp. 5703–5710, 2009.
Lämmermann T, Renkawitz J, Wu X, Hirsch K, Brakebusch C, Sixt MK. 2009. Cdc42-dependent leading edge coordination is essential for interstitial dendritic cell migration (Plenary Paper). Blood. 113(23), 5703–5710.
Lämmermann, Tim, et al. “Cdc42-Dependent Leading Edge Coordination Is Essential for Interstitial Dendritic Cell Migration (Plenary Paper).” Blood, vol. 113, no. 23, American Society of Hematology, 2009, pp. 5703–10, doi:10.1182/blood-2008-11-191882.

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