Tubulin and Microtubules

Abstract

Microtubules are found in almost all types of eukaryotic cell. Their principal constituents are the highly conserved proteins of the tubulin family, in the form of longitudinal protofilaments of tubulin heterodimers. The conserved lateral interactions produce a characteristic 2D lattice. Tubulin structure and conformational changes are now known to atomic resolution. Its GTP‐dependent dynamic self‐assembly and disassembly is modulated by a host of other proteins. This dynamic activity and a more passive role as tracks for interaction with motor proteins, kinesin and dynein, allow microtubules to perform vital roles in various forms of cell motility. They are an essential component of cell division, provide oriented tracks for the transport of cellular organelles and vesicles and are responsible for the relative positioning of cellular compartments. Thus, they are important targets in the control of cancer cells, as their essential activity is severely affected by a variety of drugs. Key Concepts Tubulin heterodimers, consisting of highly homologous α‐ and β‐tubulin monomers, self‐assemble into a unique lattice with polar longitudinal ‘protofilaments’ The assembled sheet has a slightly variable curvature, producing microtubules, with around 13 protofilaments but not strictly defined unless they are grown from a γ‐tubulin template or given a curvature appropriate to exactly 13 protofilaments by accessory proteins The structure of microtubules has been solved to near‐atomic level both with GTP homologues bound to β‐tubulin and with GDP bound; also a depolymerised protofilament structure in a longitudinally curved conformation is known Hydrolysis of bound GTP enables microtubules to assemble with ‘dynamic instability’, behaviour that depends on stochastic disassembly when the GTP ‘cap’ is lost from a growing end Microtubule behaviour is modified by many different accessory proteins that may act just at the tips or everywhere on the lattice wall To play different roles according to their positions in cells, the properties of microtubules may vary owing to different tubulin isotypes and be modified by a wide range of associated proteins Changes can also vary with time (‘ageing’) as a result of post‐translational modification of tubulin and of some accessory proteins Microtubules are employed in axonemes of cilia and flagella, where the motor protein dynein interacts with them to produce beating while other linking components help control the wave‐form Cytoplasmic microtubules provide tracks for vesicles and other cargoes driven by kinesins and cytoplasmic dynein Mitotic and meiotic spindles are assembled from microtubules, which interact with kinetochores and with multiple motor proteins Microtubules are susceptible to many small molecules that depolymerise or hyperstabilise them and thus serve as anti‐cancer drugs.