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

Janning D, Igaev M, Sündermann F, Brühmann J, Beutel O, Heinisch JJ, Bakota L, Piehler J, Junge W, Brandt R - Mol. Biol. Cell (2014)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurobiology, University of Osnabrück, D-49076 Osnabrück, Germany.

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Step-size distribution analysis and Monte Carlo simulation indicate jumps of tau between microtubules. (A) SSD analysis of >1000 pseudotrajectories indicating subpopulations of jumps between MTs. The peaks in the histogram correspond to 1 → 2, 1 → 3, and 1 → 4 hops between MTs. (B) SSD analysis of simulated pseudotrajectories at different pseudoequilibrium constants (kon*/koff). Note that the histogram at kon*/koff= 102 closely resembles the data shown in A. The Monte Carlo simulation revealed an additional peak (indicated in red), which was not resolved by imaging.
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Figure 3: Step-size distribution analysis and Monte Carlo simulation indicate jumps of tau between microtubules. (A) SSD analysis of >1000 pseudotrajectories indicating subpopulations of jumps between MTs. The peaks in the histogram correspond to 1 → 2, 1 → 3, and 1 → 4 hops between MTs. (B) SSD analysis of simulated pseudotrajectories at different pseudoequilibrium constants (kon*/koff). Note that the histogram at kon*/koff= 102 closely resembles the data shown in A. The Monte Carlo simulation revealed an additional peak (indicated in red), which was not resolved by imaging.

Mentions: We observed fast longitudinal and transversal displacements of tau in the cellular process (Figure 1B). To characterize quantitatively the displacements of tau, we calculated SSDs. Here the probability of a particle moving over a certain distance within a fixed time interval ∆t was evaluated. Figure 3A represents an SSD histogram plotted using >1000 2D pseudotrajectories for the first time step (see Materials and Methods). The SSD analysis of the pseudotrajectories revealed the presence of three peaks, at ∼95, ∼190, and ∼285 nm. Remarkably, these values correspond to the distance between the centers of neighboring MTs, reflecting hops 1 → 2 and multiples thereof (hops 1 → 3, 1 → 4; Figure 3A), indicating that tau can have multiple binding partners within a few tens of milliseconds. Note that peaks at intermediate locations, which might be expected due to different z-positions of neighboring MTs, are merged due to the 2D projection and contribute to the widening of the peaks.


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

Janning D, Igaev M, Sündermann F, Brühmann J, Beutel O, Heinisch JJ, Bakota L, Piehler J, Junge W, Brandt R - Mol. Biol. Cell (2014)

Step-size distribution analysis and Monte Carlo simulation indicate jumps of tau between microtubules. (A) SSD analysis of >1000 pseudotrajectories indicating subpopulations of jumps between MTs. The peaks in the histogram correspond to 1 → 2, 1 → 3, and 1 → 4 hops between MTs. (B) SSD analysis of simulated pseudotrajectories at different pseudoequilibrium constants (kon*/koff). Note that the histogram at kon*/koff= 102 closely resembles the data shown in A. The Monte Carlo simulation revealed an additional peak (indicated in red), which was not resolved by imaging.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4230615&req=5

Figure 3: Step-size distribution analysis and Monte Carlo simulation indicate jumps of tau between microtubules. (A) SSD analysis of >1000 pseudotrajectories indicating subpopulations of jumps between MTs. The peaks in the histogram correspond to 1 → 2, 1 → 3, and 1 → 4 hops between MTs. (B) SSD analysis of simulated pseudotrajectories at different pseudoequilibrium constants (kon*/koff). Note that the histogram at kon*/koff= 102 closely resembles the data shown in A. The Monte Carlo simulation revealed an additional peak (indicated in red), which was not resolved by imaging.
Mentions: We observed fast longitudinal and transversal displacements of tau in the cellular process (Figure 1B). To characterize quantitatively the displacements of tau, we calculated SSDs. Here the probability of a particle moving over a certain distance within a fixed time interval ∆t was evaluated. Figure 3A represents an SSD histogram plotted using >1000 2D pseudotrajectories for the first time step (see Materials and Methods). The SSD analysis of the pseudotrajectories revealed the presence of three peaks, at ∼95, ∼190, and ∼285 nm. Remarkably, these values correspond to the distance between the centers of neighboring MTs, reflecting hops 1 → 2 and multiples thereof (hops 1 → 3, 1 → 4; Figure 3A), indicating that tau can have multiple binding partners within a few tens of milliseconds. Note that peaks at intermediate locations, which might be expected due to different z-positions of neighboring MTs, are merged due to the 2D projection and contribute to the widening of the peaks.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurobiology, University of Osnabrück, D-49076 Osnabrück, Germany.

Show MeSH
Related in: MedlinePlus