Modulation of the dynamic instability of tubulin assembly by the microtubule-associated protein tau.

TLDR

Microtubule‑associated proteins such as tau modulate microtubule assembly and are essential for morphogenetic processes like axonal growth. We examined tau’s effect on microtubule polymerization by directly observing assembly and disassembly kinetics with dark‑field microscopy. Tau accelerates polymerization, suppresses catastrophe, and slows depolymerization, creating a partially stable yet dynamic microtubule state that is disrupted by MAP2 kinase phosphorylation, which reduces tau’s lattice affinity.

Abstract

Microtubule-associated proteins (MAP), such as tau, modulate the extent and rate of microtubule assembly and play an essential role in morphogenetic processes, such as axonal growth. We have examined the mechanism by which tau affects microtubule polymerization by examining the kinetics of microtubule assembly and disassembly through direct observation of microtubules using dark-field microscopy. Tau increases the rate of polymerization, decreases the rate of transit into the shrinking phase (catastrophe), and inhibits the rate of depolymerization. Tau strongly suppresses the catastrophe rate, and its ability to do so is independent of its ability to increase the elongation rate. Thus, tau generates a partially stable but still dynamic state in microtubules. This state is perturbed by phosphorylation by MAP2 kinase, which affects all three activities by lowering the affinity of tau for the microtubule lattice.