Ena/VASP proteins at the crossroads of actin nucleation pathways in dendritic cell migration.

Autor:	Visweshwaran SP; Leibniz-Forschungsinstitut für Molekulare Pharmakologie, Berlin, Germany., Nayab H; Leibniz-Forschungsinstitut für Molekulare Pharmakologie, Berlin, Germany., Hoffmann L; Leibniz-Forschungsinstitut für Molekulare Pharmakologie, Berlin, Germany., Gil M; Leibniz-Forschungsinstitut für Molekulare Pharmakologie, Berlin, Germany., Liu F; Leibniz-Forschungsinstitut für Molekulare Pharmakologie, Berlin, Germany., Kühne R; Leibniz-Forschungsinstitut für Molekulare Pharmakologie, Berlin, Germany., Maritzen T; Leibniz-Forschungsinstitut für Molekulare Pharmakologie, Berlin, Germany.; Department of Nanophysiology, Technische Universität Kaiserslautern, Kaiserslautern, Germany.
Jazyk:	angličtina
Zdroj:	Frontiers in cell and developmental biology [Front Cell Dev Biol] 2022 Oct 03; Vol. 10, pp. 1008898. Date of Electronic Publication: 2022 Oct 03 (Print Publication: 2022).
DOI:	10.3389/fcell.2022.1008898
Abstrakt:	As sentinels of our immune system dendritic cells (DCs) rely on efficient cell migration for patrolling peripheral tissues and delivering sampled antigens to secondary lymphoid organs for the activation of T-cells. Dynamic actin polymerization is key to their macropinocytic and migratory properties. Both major actin nucleation machineries, formins and the Arp2/3 complex, are critical for different aspects of DC functionality, by driving the generation of linear and branched actin filaments, respectively. However, the importance of a third group of actin nucleators, the Ena/VASP family, has not been addressed yet. Here, we show that the two family members Evl and VASP are expressed in murine DCs and that their loss negatively affects DC macropinocytosis, spreading, and migration. Our interactome analysis reveals Ena/VASP proteins to be ideally positioned for orchestrating the different actin nucleation pathways by binding to the formin mDia1 as well as to the WAVE regulatory complex, a stimulator of Arp2/3. In fact, Evl/VASP deficient murine DCs are more vulnerable to inhibition of Arp2/3 demonstrating that Ena/VASP proteins contribute to the robustness and efficiency of DC migration. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Visweshwaran, Nayab, Hoffmann, Gil, Liu, Kühne and Maritzen.)
Databáze:	MEDLINE
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