Microtubules regulate cell migration and neuronal pathfinding

While many cell types are able to generate cellular movement through the action of the actomyosin cytoskeleton alone, microtubules are important for establishing and maintaining polarity, regulating the force-generating machinery and cell adhesion. Therefore, directionally persistent cell migration and neuronal pathfinding often require microtubules. The microtubule cytoskeleton itself is organised asymmetrically to allow differential regulation of the migration machinery at the front and the rear of the cell. Microtubules position organelles such as the nucleus, the centrosome and the Golgi. Transport of mRNAs, vesicles, receptors and signalling components to the cell edges occurs along microtubules. These cargoes in turn support force generation by the actin cytoskeleton, act as a source of membrane lipids and regulate polarity signalling, adhesion, cell-cell communication and chemical gradient sensing. Microtubules themselves and especially the dynamic plus ends act as signalling platforms to control adhesion turnover and membrane protrusion. The rapid turnover of microtubules allows cells to quickly adapt to extracellular signals and change migration direction in response to guidance cues. Microtubule dynamics and organisation are in turn controlled by cortical cues. These feedback mechanisms ensure robustness and adaptation to environmental influences. Given the fundamental importance of cell migration for embryonic development, the immune system and wound healing, impaired microtubule function leads to birth defects and diseases. Likewise, drugs targeting microtubules are routinely used to prevent excessive cell migration in cancer metastasis and chronic inflammatory diseases