Tau Avoids the GTP Cap at Growing Microtubule Plus-Ends

Brian T. Castle; Kristen M. McKibben; Elizabeth Rhoades; David J. Odde

doi:10.1016/j.isci.2020.101782

Tau Avoids the GTP Cap at Growing Microtubule Plus-Ends

Brian T. Castle, Kristen M. McKibben, Elizabeth Rhoades, David J. Odde

Biomedical Engineering

Research output: Contribution to journal › Article › peer-review

9 Scopus citations

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 μM) over GMPCPP-tubulin (K_D = 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 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.

Original language	English (US)
Article number	101782
Journal	iScience
Volume	23
Issue number	12
DOIs	https://doi.org/10.1016/j.isci.2020.101782
State	Published - Dec 18 2020

Bibliographical note

Funding Information:
Research reported in this publication was supported by the National Institute of Aging of the National Institutes of Health under award number RF1AG053951 to E.R and D.J.O. and Institutional Training Grant T32 GM071399 to K.M.M. The authors thank Virginia Lee at the University of Pennsylvania and Lynne Cassimeris at Lehigh University for providing fluorescent protein plasmids and also thank Jonathan Sachs and Mahya Hemmat for helpful discussions.

Publisher Copyright:
© 2020 The Authors

Keywords

Cellular Neuroscience
Molecular Biology Experimental Approach
Optical Imaging

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title = "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 (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 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.",

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N2 - 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 (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 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.

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Tau Avoids the GTP Cap at Growing Microtubule Plus-Ends

Abstract

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