Plus-End-Tracking Proteins and Their Interactions at Microtubule Ends

Microtubules are cytoskeletal elements that are essential for a large number of intracellular processes, including mitosis, cell differentiation and migration, and vesicle transport. In many cells, the microtubule network is organized in a radial manner, with one end of a microtubule (the minus end) embedded near the nucleus and the other end (the plus end) exploring cytoplasmic space, switching between episodes of growth and shrinkage. Mammalian plus-end-tracking proteins (+TIPs) localize to the ends of growing microtubules and regulate both the dynamic behavior of microtubules as well as the interactions of microtubules with other cellular components. Because of these crucial roles, +TIPs and the mechanisms underlying their association with microtubule ends have been intensively investigated. Results indicate that +TIPs reach microtubule ends by motor-mediated transport or diffusion. Individual +TIP molecules exchange rapidly on microtubule end-binding sites that are formed during microtubule polymerization and that have a slower turnover. Most +TIPs associate with the end-binding (EB) proteins, and appear to require these 'core' +TIPs for localization at microtubule ends. Accumulation of +TIPs may also involve structural features of the microtubule end and interactions with other +TIPs. This complexity makes it difficult to assign discrete roles to specific +TIPs. Given that +TIPs concentrate at microtubule ends and that each +TIP binds in a conformationally distinct manner, I propose that the ends of growing microtubules are 'nano-platforms' for productive interactions between selected proteins and that these interactions might persist and be functional elsewhere in the cytoplasm than at the microtubule end at which they originated.

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