Innate control of actin nucleation determines two distinct migration behaviours in dendritic cells

Pablo Vargas, Paolo Maiuri, Marine Bretou, Pablo J. Saéz, Paolo Pierobon, Mathieu Maurin, Mélanie Chabaud, Danielle Lankar, Dorian Obino, Emmanuel Terriac, Matthew Raab, Hawa Racine Thiam, Thomas Brocker, Susan M. Kitchen-Goosen, Arthur S. Alberts, Praveen Sunareni, Sheng Xia, Rong Li, Raphael Voituriez, Matthieu PielAna Maria Lennon-Duménil

Research output: Contribution to journalArticle

Abstract

Dendritic cell (DC) migration in peripheral tissues serves two main functions: antigen sampling by immature DCs, and chemokine-guided migration towards lymphatic vessels (LVs) on maturation. These migratory events determine the efficiency of the adaptive immune response. Their regulation by the core cell locomotion machinery has not been determined. Here, we show that the migration of immature DCs depends on two main actin pools: a RhoA-mDia1-dependent actin pool located at their rear, which facilitates forward locomotion; and a Cdc42-Arp2/3-dependent actin pool present at their front, which limits migration but promotes antigen capture. Following TLR4-MyD88-induced maturation, Arp2/3-dependent actin enrichment at the cell front is markedly reduced. Consequently, mature DCs switch to a faster and more persistent mDia1-dependent locomotion mode that facilitates chemotactic migration to LVs and lymph nodes. Thus, the differential use of actin-nucleating machineries optimizes the migration of immature and mature DCs according to their specific function.

Original languageEnglish (US)
Pages (from-to)43-53
Number of pages11
JournalNature cell biology
Volume18
Issue number1
DOIs
StatePublished - Jan 1 2016

ASJC Scopus subject areas

  • Cell Biology

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    Vargas, P., Maiuri, P., Bretou, M., Saéz, P. J., Pierobon, P., Maurin, M., Chabaud, M., Lankar, D., Obino, D., Terriac, E., Raab, M., Thiam, H. R., Brocker, T., Kitchen-Goosen, S. M., Alberts, A. S., Sunareni, P., Xia, S., Li, R., Voituriez, R., ... Lennon-Duménil, A. M. (2016). Innate control of actin nucleation determines two distinct migration behaviours in dendritic cells. Nature cell biology, 18(1), 43-53. https://doi.org/10.1038/ncb3284