Long-range microtubule guidance

In moving cells, dynamic microtubules (MTs) are targeted to focal adhesion (FA) sites, where their cargo mediates FA disassembly to allow the cell to detach from the substrate and propel itself forwards. Although MTs have been frequently observed at focal adhesions (FAs), their spatial overlap has thus far precluded the analysis of the mechanisms that guide the growing MTs through the cell to reach FAs at the cell periphery. On page 5790, Bartosz Grzybowski and colleagues controlled the cell geometry to remove this spatial overlap, in order to allow an unambiguous analysis of MT guidance to FAs. Specifically, these cells are confined to adhesive triangular microislands, which determine cell shape and ensure that FAs localise exclusively to the vertices of the triangles. Using a combination of high-resolution imaging and RNAi-mediated gene depletion, the authors show that initial MT nucleation occurs at the centrosome without any directional preference. However, with increasing distance from the centrosome, the trajectories of MTs that grow along F-actin bundles align with FAs at the vertices, suggesting that a non-random, active FA-mediated guiding mechanism is at play. Consequently, in the absence of FAs, MT growth is unguided. Furthermore, when either myosin IIA or myosin IIB is depleted, thereby removing F-actin bundles, MT growth also becomes random. These results suggest that MT guidance is controlled by a long-range mechanism that acts throughout the entire cell.