摘要：SummaryPlus-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 (KD = 0.26 μM) over GMPCPP-tubulin (KD = 1.1 μM)in vitro,as well as GTP-tubulin at the tips of growing microtubules, causing tau binding to lag behind the plus-end bothin vitroand 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.Graphical AbstractDisplay OmittedHighlights•Tau binds stronger to GDP-containing over GMPCPP-containing microtubulesin vitro•Tau preferentially binds the microtubule lattice over the tipin vitroand in cells•Due to microtubule tip avoidance, tau primarily acts to inhibit shorteningOptical Imaging; Molecular Biology Experimental Approach; Cellular Neuroscience
