B cell mechanotransduction via ATAT1 coordinates actin and lysosomal dynamics at the immune synapse

: Aceiton, Pablo; Riobo, Isidora; Del Valle Batalla, Felipe; Diaz-Munoz, Jheimmy; Ulloa, Romina; Cabrera Reyes, Fernanda; Contreras, Teemly; Hernandez-Perez, Sara; Mattila, Pieta K.; Yuseff, Maria Isabel

Publisher: Rockefeller University Press

: NEW YORK

: 2025

: Journal of Cell Biology

: J CELL BIOL

: e202407181

: 224

: 8

: 23

: 0021-9525

: 1540-8140

DOI: https://doi.org/10.1083/jcb.202407181

: https://doi.org/10.1083/jcb.202407181

B cells extract immobilized antigens via immune synapse formation, a process influenced by the physical properties of the antigen-presenting surface. However, the mechanisms linking mechanotransduction to antigen extraction and processing remain poorly understood. Here, we show that B cells activated on stiff substrates initiate mechanotransduction responses that drive the translocation of the microtubule acetylase ATAT1 from the nucleus to the cytoplasm, leading to increased alpha-tubulin acetylation. This modification releases GEF-H1 at the immune synapse, where it promotes the formation of actin foci essential for antigen extraction. Acetylated microtubules also enable B cells to stabilize and position lysosomes at the synapse center, thereby coupling actin-dependent extraction to antigen processing and presentation. Accordingly, ATAT1-silenced B cells fail to concentrate actin foci and lysosomes at the synaptic interface, resulting in impaired antigen extraction and presentation to T cells. Overall, these findings underscore how BCR-dependent mechanotransduction induces microtubule modifications to orchestrate lysosome positioning and actin remodeling at the immune synapse.

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This work was supported by ANID-FONDECYT grant #1221128 for M.I. Yuseff, ANID Ph.D. national scholarship #21191062 for F. Del Valle Batalla, and the Research Council of Finland (grant #339810 to P.K. Mattila). F. Del Valle Batalla and M.I. Yuseff thank all members of the P.K. Mattila lab for their constructive feedback on this work. We also thank Martina Alamo from the M.I. Yuseff lab for her useful advice concerning experimental procedures and ideas for new approaches.