Dynamic microtubules as sensors in animal cells.

Microtubules physically organize eukaryotic cells by serving as structural elements and polarized transport tracks. This article advances the hypothesis that dynamic microtubules also serve as sensors of cell shape and cytoplasmic state, building on ideas proposed for higher plant cells. Microtubule polymerization dynamics and lattice structure are sensitive to mechanical, chemical, and signaling inputs that alter the balance between microtubules and soluble tubulin and regulate MAP binding affinity. These changes are detected by transducers, which include the GTP exchange factor GEF-H1 (ARHGEF2) and MARK family kinases. The resulting signals regulate cytoplasmic behavior, gene expression, and tissue physiology. The microtubule-destabilizing drugs colchicine and plinabulin may mimic sensing of pathophysiological cues by microtubules, leading to activation of gene expression programs that promote cell survival, growth, and repair, which account for the therapeutic actions of the drugs. In tissue cells with stable morphologies, the sensory functions of microtubules may be as or more important than their architectural functions. This reframing of microtubule biology suggests new directions for mechanistic inquiry and drug discovery.