Microtubules coordinate protrusion-retraction dynamics in migrating dendritic cells

When traversing complex microenvironments, migrating cells extend multiple exploratory protrusions into the interstitial space. In order to preserve cell integrity and maintain polarity as the cell advances, supernumerary protrusions and tethered trailing edges need to be retracted in a coordinated fashion. Here, we demonstrate that spatially distinct microtubule dynamics regulate cell migration by locally specifying the retraction of explorative protrusions. We found that in migrating dendritic cells, local microtubule depolymerization triggers myosin II dependent contractility via the RhoA GEF Lfc. Depletion of Lfc leads to aberrant myosin localization, thereby causing two effects that rate-limit locomotion: i) defective adhesion-resolution and ii) impaired cell edge coordination during path-finding. Such compromised cell shape coordination is particularly hindering when cells navigate through geometrically complex microenvironments, where it leads to entanglement and ultimately fragmentation of the cell body. Our data demonstrate that microtubules regulate dendritic cell shape and coherence by local control of protrusion-retraction dynamics.