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Single-molecule tracking of tau reveals fast kiss-and-hop interaction with microtubules in living neurons
The microtubule-associated phosphoprotein tau regulates microtubule dynamics and is involved in neurodegenerative diseases collectively called tauopathies. It is generally believed that the vast majority of tau molecules decorate axonal microtubules, thereby stabilizing them. However, it is an open...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4230615/ https://www.ncbi.nlm.nih.gov/pubmed/25165145 http://dx.doi.org/10.1091/mbc.E14-06-1099 |
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author | Janning, Dennis Igaev, Maxim Sündermann, Frederik Brühmann, Jörg Beutel, Oliver Heinisch, Jürgen J. Bakota, Lidia Piehler, Jacob Junge, Wolfgang Brandt, Roland |
author_facet | Janning, Dennis Igaev, Maxim Sündermann, Frederik Brühmann, Jörg Beutel, Oliver Heinisch, Jürgen J. Bakota, Lidia Piehler, Jacob Junge, Wolfgang Brandt, Roland |
author_sort | Janning, Dennis |
collection | PubMed |
description | The microtubule-associated phosphoprotein tau regulates microtubule dynamics and is involved in neurodegenerative diseases collectively called tauopathies. It is generally believed that the vast majority of tau molecules decorate axonal microtubules, thereby stabilizing them. However, it is an open question how tau can regulate microtubule dynamics without impeding microtubule-dependent transport and how tau is also available for interactions other than those with microtubules. Here we address this apparent paradox by fast single-molecule tracking of tau in living neurons and Monte Carlo simulations of tau dynamics. We find that tau dwells on a single microtubule for an unexpectedly short time of ∼40 ms before it hops to the next. This dwell time is 100-fold shorter than previously reported by ensemble measurements. Furthermore, we observed by quantitative imaging using fluorescence decay after photoactivation recordings of photoactivatable GFP–tagged tubulin that, despite this rapid dynamics, tau is capable of regulating the tubulin–microtubule balance. This indicates that tau's dwell time on microtubules is sufficiently long to influence the lifetime of a tubulin subunit in a GTP cap. Our data imply a novel kiss-and-hop mechanism by which tau promotes neuronal microtubule assembly. The rapid kiss-and-hop interaction explains why tau, although binding to microtubules, does not interfere with axonal transport. |
format | Online Article Text |
id | pubmed-4230615 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-42306152015-01-20 Single-molecule tracking of tau reveals fast kiss-and-hop interaction with microtubules in living neurons Janning, Dennis Igaev, Maxim Sündermann, Frederik Brühmann, Jörg Beutel, Oliver Heinisch, Jürgen J. Bakota, Lidia Piehler, Jacob Junge, Wolfgang Brandt, Roland Mol Biol Cell Articles The microtubule-associated phosphoprotein tau regulates microtubule dynamics and is involved in neurodegenerative diseases collectively called tauopathies. It is generally believed that the vast majority of tau molecules decorate axonal microtubules, thereby stabilizing them. However, it is an open question how tau can regulate microtubule dynamics without impeding microtubule-dependent transport and how tau is also available for interactions other than those with microtubules. Here we address this apparent paradox by fast single-molecule tracking of tau in living neurons and Monte Carlo simulations of tau dynamics. We find that tau dwells on a single microtubule for an unexpectedly short time of ∼40 ms before it hops to the next. This dwell time is 100-fold shorter than previously reported by ensemble measurements. Furthermore, we observed by quantitative imaging using fluorescence decay after photoactivation recordings of photoactivatable GFP–tagged tubulin that, despite this rapid dynamics, tau is capable of regulating the tubulin–microtubule balance. This indicates that tau's dwell time on microtubules is sufficiently long to influence the lifetime of a tubulin subunit in a GTP cap. Our data imply a novel kiss-and-hop mechanism by which tau promotes neuronal microtubule assembly. The rapid kiss-and-hop interaction explains why tau, although binding to microtubules, does not interfere with axonal transport. The American Society for Cell Biology 2014-11-05 /pmc/articles/PMC4230615/ /pubmed/25165145 http://dx.doi.org/10.1091/mbc.E14-06-1099 Text en © 2014 Janning, Igaev, et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology. |
spellingShingle | Articles Janning, Dennis Igaev, Maxim Sündermann, Frederik Brühmann, Jörg Beutel, Oliver Heinisch, Jürgen J. Bakota, Lidia Piehler, Jacob Junge, Wolfgang Brandt, Roland Single-molecule tracking of tau reveals fast kiss-and-hop interaction with microtubules in living neurons |
title | Single-molecule tracking of tau reveals fast kiss-and-hop interaction with microtubules in living neurons |
title_full | Single-molecule tracking of tau reveals fast kiss-and-hop interaction with microtubules in living neurons |
title_fullStr | Single-molecule tracking of tau reveals fast kiss-and-hop interaction with microtubules in living neurons |
title_full_unstemmed | Single-molecule tracking of tau reveals fast kiss-and-hop interaction with microtubules in living neurons |
title_short | Single-molecule tracking of tau reveals fast kiss-and-hop interaction with microtubules in living neurons |
title_sort | single-molecule tracking of tau reveals fast kiss-and-hop interaction with microtubules in living neurons |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4230615/ https://www.ncbi.nlm.nih.gov/pubmed/25165145 http://dx.doi.org/10.1091/mbc.E14-06-1099 |
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