Microtubules control cellular shape and coherence in amoeboid migrating cells

Aglaja Kopf, Jörg Renkawitz, Robert Hauschild, Irute Girkontaite, Kerry Tedford, Jack Merrin, Oliver Thorn-Seshold, Dirk Trauner, Hans Häcker, Klaus Dieter Fischer, Eva Kiermaier, Michael Sixt

Research output: Contribution to journalArticle

Abstract

Cells navigating through complex tissues face a fundamental challenge: while multiple protrusions explore different paths, the cell needs to avoid entanglement. How a cell surveys and then corrects its own shape is poorly understood. Here, we demonstrate that spatially distinct microtubule dynamics regulate amoeboid cell migration by locally promoting the retraction of protrusions. In migrating dendritic cells, local microtubule depolymerization within protrusions remote from the microtubule organizing center triggers actomyosin contractility controlled by RhoA and its exchange factor Lfc. Depletion of Lfc leads to aberrant myosin localization, thereby causing two effects that rate-limit locomotion: (1) impaired cell edge coordination during path finding and (2) defective adhesion resolution. Compromised shape control is particularly hindering in geometrically complex microenvironments, where it leads to entanglement and ultimately fragmentation of the cell body. We thus demonstrate that microtubules can act as a proprioceptive device: they sense cell shape and control actomyosin retraction to sustain cellular coherence.

Original languageEnglish (US)
Article numbere201907154
JournalJournal of Cell Biology
Volume219
Issue number6
DOIs
StatePublished - Jan 1 2020

ASJC Scopus subject areas

  • Cell Biology

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    Kopf, A., Renkawitz, J., Hauschild, R., Girkontaite, I., Tedford, K., Merrin, J., Thorn-Seshold, O., Trauner, D., Häcker, H., Fischer, K. D., Kiermaier, E., & Sixt, M. (2020). Microtubules control cellular shape and coherence in amoeboid migrating cells. Journal of Cell Biology, 219(6), [e201907154]. https://doi.org/10.1083/JCB.201907154