Tau Avoids the GTP Cap at Growing Microtubule Plus-Ends.

ABSTRACT: Plus-end tracking proteins (+TIPs) associate with the growing end of microtubules and mediate important cellular functions. The majority of +TIPs are directed to the plus-end through a family of end-binding proteins (EBs), which preferentially bind the stabilizing cap of GTP-tubulin present during microtubule growth. One outstanding question is whether there may exist other microtubule-associated proteins (MAPs) that preferentially bind specific nucleotide states of tubulin. Here, we report that the neuronal MAP tau preferentially binds GDP-tubulin (K _D = 0.26 ?M) over GMPCPP-tubulin (K _D = 1.1 ?M) in vitro, as well as GTP-tubulin at the tips of growing microtubules, causing tau binding to lag behind the plus-end both in vitro and in live cells. Thus, tau is a microtubule tip avoiding protein, establishing the framework for a possible new class of tip avoiding MAPs. We speculate that disease-relevant tau mutations may exert their phenotype by their failure to properly recognize GDP-tubulin.

SUBMITTER: Castle BT 

PROVIDER: S-EPMC7691178 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature