Control of microtubule organization and dynamics: two ends in the limelight

Key Points Microtubule organization and dynamics are controlled by proteins that associate with the two microtubule extremities, the plus end and the minus end. Proteins accumulating at microtubule ends can promote or inhibit microtubule polymerization, enhance or block microtubule disassembly, or induce transitions between microtubule growth and shortening. Microtubule plus-end-tracking proteins (+TIPs) can accumulate at microtubule ends by recognizing the stabilizing GTP cap at growing microtubule tips or the curvature of the outermost part of the microtubule, or by plus-end-directed motor activity. This accumulation can be enhanced by electrostatic interactions between positively charged protein domains and the negatively charged microtubule lattice. +TIPs form extensive interaction networks, which depend on a limited number of protein motifs and modules that bind to each other with moderate affinity, allowing rapid remodelling of the end-associated complexes during microtubule growth and shortening. The recruitment of proteins with SxIP and cytoskeleton-associated protein Gly-rich (CAP-Gly) domains by the 'autonomous' +TIPs of the end-binding protein (EB) family plays a major part in the formation of these networks. +TIP networks are responsible for a large range of cellular functions, such as microtubule guidance along other cytoskeletal elements, microtubule attachment to the cell cortex, kinetochores and intracellular membrane organelles, positioning of microtubule arrays and signalling. Microtubule minus-end-targeting proteins (−TIPs) of the calmodulin-regulated spectrin-associated protein (CAMSAP) and Patronin family accumulate at free, growing microtubule minus ends and control the architecture of microtubule networks by stabilizing non-centrosomal microtubules. A wide range of diverse pharmacological agents can target microtubule tips either directly or indirectly and cooperate with +TIPs in regulating the dynamics of microtubule ends. Microtubule plus ends and minus ends accumulate specific sets of proteins that can regulate microtubule dynamics, connect microtubules to cellular structures and recruit signalling molecules that collectively control cellular behaviour. Our knowledge of the factors that associate with microtubule ends, and the mechanisms through which they do this, has strongly increased in recent years. Microtubules have fundamental roles in many essential biological processes, including cell division and intracellular transport.