Promoting microtubule assembly: a hypothesis for the functional significance of the +TIP network

Regulation of microtubule (MT) dynamics is essential for many cellular processes, but the machinery that controls MT dynamics remains poorly understood. MT plus-end tracking proteins (+TIPs) are a set of MT-associated proteins that dynamically track growing MT ends and are uniquely positioned to govern MT dynamics. +TIPs associate with each other in a complex array of inter- and intra-molecular interactions known as the "+TIP network." Why do so many +TIPs bind to other +TIPs? Typical answers include the ideas that these interactions localize proteins where they are needed, deliver proteins to the cortex, and/or create regulatory pathways. We propose an additional and more mechanistic hypothesis: that +TIPs bind each other to create a superstructure that promotes MT assembly by constraining the structural fluctuations of the MT tip, thus acting as a polymerization chaperone. +TIPs are a set of microtubule-associated proteins that dynamically track growing microtubule plus-ends and are considered master controllers of microtubule dynamics. Here, we propose that the network of interactions between +TIPs creates a superstructure that promotes microtubule assembly by constraining the structural fluctuations of the microtubule tips.