title: Single-molecule tracking of tau reveals fast kiss-and-hop interaction with microtubules in living neurons.
abstract: 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.
authors.affiliation: Department of Neurobiology, University of Osnabrück, D-49076 Osnabrück, Germany.
authors.forename: Dennis
authors.initials: D
authors.lastname: Janning
authors.affiliation: Department of Neurobiology, University of Osnabrück, D-49076 Osnabrück, Germany.
authors.forename: Maxim
authors.initials: M
authors.lastname: Igaev
authors.affiliation: Department of Neurobiology, University of Osnabrück, D-49076 Osnabrück, Germany.
authors.forename: Frederik
authors.initials: F
authors.lastname: Sündermann
authors.affiliation: Department of Neurobiology, University of Osnabrück, D-49076 Osnabrück, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Brühmann
authors.affiliation: Department of Biophysics, University of Osnabrück, D-49076 Osnabrück, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Beutel
authors.affiliation: Department of Genetics, University of Osnabrück, D-49076 Osnabrück, Germany.
authors.forename: Jürgen J
authors.initials: JJ
authors.lastname: Heinisch
authors.affiliation: Department of Neurobiology, University of Osnabrück, D-49076 Osnabrück, Germany.
authors.forename: Lidia
authors.initials: L
authors.lastname: Bakota
authors.affiliation: Department of Biophysics, University of Osnabrück, D-49076 Osnabrück, Germany.
authors.forename: Jacob
authors.initials: J
authors.lastname: Piehler
authors.affiliation: Department of Biophysics, University of Osnabrück, D-49076 Osnabrück, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Junge
authors.affiliation: Department of Neurobiology, University of Osnabrück, D-49076 Osnabrück, Germany brandt@biologie.uni-osnabrueck.de.
authors.forename: Roland
authors.initials: R
authors.lastname: Brandt
mesh_terms: D000818:Animals; D001370:Axonal Transport; D001369:Axons / Q000378:metabolism*; D002454:Cell Differentiation; D015870:Gene Expression; D017930:Genes, Reporter; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D007700:Kinetics; D016086:Lentivirus / Q000235:genetics; D008856:Microscopy, Fluorescence; D008870:Microtubules / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D056004:Molecular Dynamics Simulation; D057054:Molecular Imaging; D009010:Monte Carlo Method; D016716:PC12 Cells; D051381:Rats; D015398:Signal Transduction / Q000235:genetics*; D014404:Tubulin / Q000737:chemistry / Q000378:metabolism*; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D014404:Tubulin; D016875:tau Proteins; D049452:Green Fluorescent Proteins