Microtubules control cellular shape and coherence in amoeboid migrating cells

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.

Huntington’s Disease—An Outlook on the Interplay of the HTT Protein, Microtubules and Actin Cytoskeletal Components

“…In addition, several factors act as cross-linkers of the two filament systems, providing a mechanism for their property changes, interrelationship within a wide range of functions. Morphological changes during the development and functioning of the nervous system are the result of a complex interplay of the MT system and actin filaments in the neuron [ 2 ], and in this sense, the neuron is no different from other types of cells [ 3 , 4 , 5 ].…”

Amplified centrosomes in dendritic cells promote immune cell effector functions

“…Fast transport of MHC class II containing vesicles to the cell surface is accomplished along MT filaments 33,49 . During DC migration, MTs control pathfinding and coordination of multiple protrusions in complex 3D environments as well as maintenance of cell coherence 13,30 . Upon arrival in lymph nodes, DCs and T lymphocytes engage with each other at a structure termed immunological synapse, which allows transmission of different types of signals.…”

Photoswitchable paclitaxel-based microtubule stabilisers allow optical control over the microtubule cytoskeleton

“…We here focus on the microtubule (MT) cytoskeleton. MTs play particularly important roles in intracellular transport, cell motility and morphological plasticity, and there is a conspicuous need to achieve a better understanding of how these many functions are implemented and regulated 4 , 5 . The role of MT dynamics during cell proliferation has also made them a major anticancer target, for which several outstanding drugs (taxanes, epothilones and vinca alkaloids) have been developed 6 – 8 .…”