Tracking the ends: a dynamic protein network controls the fate of microtubule tips

Key Points Plus-end tracking proteins (+TIPs) are distinguished by their ability to specifically accumulate at the growing ends of microtubules. +TIPs include several structurally unrelated and evolutionary conserved protein families of microtubule-associated proteins (MAPs). Several relatively small protein modules and linear sequence motifs, including calponin homology domains, CAP-Gly domains, C-terminal acidic-aromatic motifs, basic, Ser-rich sequence stretches and coiled-coil domains are present in many +TIPs and mediate interactions of these proteins with each other and with microtubules. These interactions are usually of moderate affinity allowing dynamic +TIP networks to remodel rapidly. Although many +TIPs directly interact with each other, they can exert different and sometimes opposite effects on microtubule dynamics, such as microtubule stabilization or destabilization. Molecular mechanisms that underlie microtubule plus-end tracking phenomena are not yet fully resolved. They probably involve the recognition of some specific tubulin sites, which are exposed only at the growing ends of microtubules but are shielded within the microtubule lattice. +TIPs may be recruited to microtubule ends by diffusion through cytoplasm or along the microtubule lattice; by co-polymerization with tubulin subunits or by motor-mediated transport along the microtubules. +TIP accumulation at the growing microtubule ends can serve both structural and signalling purposes. +TIPs can affect the shape and positioning of microtubule networks by regulating microtubule dynamics, by linking microtubules to different cellular structures and by exerting forces at the microtubule ends. Therefore, +TIPs are profoundly involved in many processes such as cell division, polarity and differentiation, and morphogenesis. How do cytoskeletal components interact to control cellular processes? At the growing microtubule plus ends, microtubule plus-end tracking proteins (+TIPs) regulate different aspects of cell architecture by controlling microtubule dynamics, microtubule interactions with cellular structures and signalling factors, and forces exerted on microtubule networks. Microtubule plus-end tracking proteins (+TIPs) are a diverse group of evolutionarily conserved cellular factors that accumulate at the ends of growing microtubules. They form dynamic networks through the interaction of a limited set of protein modules, repeat sequences and linear motifs that bind to each other with mo