Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Janning, Dennis, Igaev, Maxim, Sündermann, Frederik, Brühmann, Jörg, Beutel, Oliver, Heinisch, Jürgen J., Bakota, Lidia, Piehler, Jacob, Junge, Wolfgang, Brandt, Roland
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2014
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
_version_ 1782344300754894848
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
work_keys_str_mv AT janningdennis singlemoleculetrackingoftaurevealsfastkissandhopinteractionwithmicrotubulesinlivingneurons
AT igaevmaxim singlemoleculetrackingoftaurevealsfastkissandhopinteractionwithmicrotubulesinlivingneurons
AT sundermannfrederik singlemoleculetrackingoftaurevealsfastkissandhopinteractionwithmicrotubulesinlivingneurons
AT bruhmannjorg singlemoleculetrackingoftaurevealsfastkissandhopinteractionwithmicrotubulesinlivingneurons
AT beuteloliver singlemoleculetrackingoftaurevealsfastkissandhopinteractionwithmicrotubulesinlivingneurons
AT heinischjurgenj singlemoleculetrackingoftaurevealsfastkissandhopinteractionwithmicrotubulesinlivingneurons
AT bakotalidia singlemoleculetrackingoftaurevealsfastkissandhopinteractionwithmicrotubulesinlivingneurons
AT piehlerjacob singlemoleculetrackingoftaurevealsfastkissandhopinteractionwithmicrotubulesinlivingneurons
AT jungewolfgang singlemoleculetrackingoftaurevealsfastkissandhopinteractionwithmicrotubulesinlivingneurons
AT brandtroland singlemoleculetrackingoftaurevealsfastkissandhopinteractionwithmicrotubulesinlivingneurons