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J Cell Biol . 2020 Jun 1;

Microtubules control cellular shape and coherence in amoeboid migrating cells

Christian Kurts, Florent Ginhoux, Ulf Panzer, Elena Mitsi, Beatriz Carniel, Jesús Reiné, Jamie Rylance, Seher Zaidi, Alessandra Soares-Schanoski, Victoria Connor, Andrea M Collins, Andreas Schlitzer, Elissavet Nikolaou, Carla Solórzano, Sherin Pojar, Helen Hill, Angela D Hyder-Wright, Kondwani C Jambo, Marco R Oggioni, Megan De Ste Croix, Stephen B Gordon, Simon P Jochems, Daniela M Ferreira, Stephanie Fischinger, Jonathan K Fallon, Ashlin R Michell, Thomas Broge, Todd J Suscovich, Hendrik Streeck, Galit Alter, Laura Schaupp, Sabine Muth, Leif Rogell, Michael Kofoed-Branzk, Felix Melchior, Stefan Lienenklaus, Stephanie C Ganal-Vonarburg, Matthias Klein, Fabian Guendel, Tobias Hain, Kristian Schütze, Ulrike Grundmann, Vanessa Schmitt, Martina Dorsch, Julia Spanier, Pia-Katharina Larsen, Thomas Schwanz, Sven Jäckel, Christoph Reinhardt, Tobias Bopp, Sven Danckwardt, Karsten Mahnke, Gitta Anne Heinz, Mir-Farzin Mashreghi, Pawel Durek, Ulrich Kalinke, Oliver Kretz, Tobias B Huber, Siegfried Weiss, Christoph Wilhelm, Andrew J Macpherson, Hansjörg Schild, Andreas Diefenbach, Hans Christian Probst, 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

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.

PMID: 32379884