Single-molecule tracking of tau reveals fast kiss-and-hop interaction with microtubules in living neurons

Autor(en): Janning, Dennis
Igaev, Maxim
Suendermann, Frederik
Bruehmann, Joerg
Beutel, Oliver
Heinisch, Juergen J.
Bakota, Lidia
Piehler, Jacob 
Junge, Wolfgang 
Brandt, Roland 
Stichwörter: ALZHEIMERS-DISEASE; BINDING; Cell Biology; CELLS; GROWTH; LOCALIZATION; MEMBRANE; MESSENGER-RNA; ORGANIZATION; PROTEIN-TAU; TRANSPORT
Erscheinungsdatum: 2014
Herausgeber: AMER SOC CELL BIOLOGY
Journal: MOLECULAR BIOLOGY OF THE CELL
Volumen: 25
Ausgabe: 22, SI
Startseite: 3541
Seitenende: 3551
Zusammenfassung: 
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 similar to 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.
ISSN: 10591524
DOI: 10.1091/mbc.E14-06-1099

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