Regulation of cell migration by dynamic microtubules

Abstract

Microtubules define the architecture and internal organization of cells by positioning organelles and activities, as well as by supporting cell shape and mechanics. One of the major functions of microtubules is the control of polarized cell motility. In order to support the asymmetry of polarized cells, microtubules have to be organized asymmetrically themselves. Asymmetry in microtubule distribution and stability is regulated by multiple molecular factors, most of which are microtubule-associated proteins that locally control microtubule nucleation and dynamics. At the same time, the dynamic state of microtubules is key to the regulatory mechanisms by which microtubules regulate cell polarity, modulate cell adhesion and control force-production by the actin cytoskeleton. Here, we propose that even small alterations in microtubule dynamics can influence cell migration via several different microtubule-dependent pathways. We discuss regulatory factors, potential feedback mechanisms due to functional microtubule-actin crosstalk and implications for cancer cell motility.

Figure 1

Polarized regulation of microtubule dynamics and molecular factors asymmetrically regulated and/or positioned by microtubules at the front or rear of motile cell. Background: asymmetric microtubule cytoskeleton of a Swiss 3T3 fibroblast visualised by tubulin immunostaining.

Figure 2

Putative mechanisms of microtubule dynamics-mediated control of protein localisation and activity.