MICROTUBULE RETRACTION INTO THE UROPOD AND ITS ROLE IN T-CELL POLARIZATION AND MOTILITY

Spherical circulating T cells must polarize to extravasate. We have fo und that the polarization process includes a drastic reconfiguration o f the tubulin cytoskeleton. In spherical T cells, the nucleus is surro unded 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 c arried in its distal tip, The attached microtubules retract into the u ropod 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, Inste ad, the data suggest that retraction of the relatively rigid microtubu les into the streamlined uropod increases T cell deformability, thereb y facilitating migration through constricted spaces, Microtubule retra ction, therefore, may prove to be a strategy for accelerating extravas ation without disassembly of the microtubule-based transport system.