Microtubule retraction into the uropod and its role in T cell polarization and motility

Abstract

Spherical circulating T cells must polarize to extravasate. We have found that the polarization process includes a drastic reconfiguration of the tubulin cytoskeleton. In spherical T cells, the nucleus is surrounded by microtubules radiating from the microtubule organizing center (MTOC). During polarization the uropod (a slender posterior appendage) forms at the site of the MTOC. As the uropod buds out, the MTOC is carried in its distal tip. The attached microtubules retract into the uropod lumen, collapsing like the spokes of an umbrella into a compact sheaf. Experiments with microtubule inhibitors show that the retracted microtubules do not support the uropod or produce motive force. Instead, the data suggest that retraction of the relatively rigid microtubules into the streamlined uropod increases T cell deformability, thereby facilitating migration through constricted spaces. Microtubule retraction, therefore, may prove to be a strategy for accelerating extravasation without disassembly of the microtubule-based transport system.