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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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Related in: MedlinePlus

Tau interacts with multiple microtubules in processes of PC12 cells. (A) Schematic representation showing the geometry and MT distribution in a process of a neuronally differentiated PC12 cell. (B) Localization of a single Halo-tau molecule in a PC12 cell process over time (for a high-resolution version see Supplemental Figure S1). For comparison, thickness and density of MTs are schematically indicated by green bars. Top, enlargement of the indicated segment. (C) Schematic representation of a real trajectory of a molecule moving between microtubules in a bundle is shown in black. Yellow and black circles indicate binding events of tau with microtubules. The recorded pseudotrajectory is indicated in red. Only the binding events within the time frame (Δt) are detected and indicated by the yellow circles. (D) Time series showing the movement of a syp-mCherry–tagged vesicle in a PC12 cell process. In contrast to tau, localization of syp-mCherry over time indicates directional movement along a single MT. Scale bar, 1 μm.
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Figure 2: Tau interacts with multiple microtubules in processes of PC12 cells. (A) Schematic representation showing the geometry and MT distribution in a process of a neuronally differentiated PC12 cell. (B) Localization of a single Halo-tau molecule in a PC12 cell process over time (for a high-resolution version see Supplemental Figure S1). For comparison, thickness and density of MTs are schematically indicated by green bars. Top, enlargement of the indicated segment. (C) Schematic representation of a real trajectory of a molecule moving between microtubules in a bundle is shown in black. Yellow and black circles indicate binding events of tau with microtubules. The recorded pseudotrajectory is indicated in red. Only the binding events within the time frame (Δt) are detected and indicated by the yellow circles. (D) Time series showing the movement of a syp-mCherry–tagged vesicle in a PC12 cell process. In contrast to tau, localization of syp-mCherry over time indicates directional movement along a single MT. Scale bar, 1 μm.

Mentions: The spatial resolution of single-molecule tracking (∼20 nm) was high enough to discriminate between tau being attached to one particular MT or to its neighbor in processes of PC12 cells (Figure 2A). Note that the spacing between MTs in PC12 neurites is ∼70 nm (Jacobs and Stevens, 1986), a much higher value than the typical MT–MT distance in axons (Hirokawa and Takemura, 2005) due to the fact that PC12 cells do not develop axonal compartmentalization. Figure 2B (see also Supplemental Movie S2) documents the “pseudotrajectory” of binding events of tau over time (for a real trajectory, see Figure 2C). It is also evident that tau binds to several neighboring MTs in the transversal direction during the recording time (Figure 2B).


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)

Tau interacts with multiple microtubules in processes of PC12 cells. (A) Schematic representation showing the geometry and MT distribution in a process of a neuronally differentiated PC12 cell. (B) Localization of a single Halo-tau molecule in a PC12 cell process over time (for a high-resolution version see Supplemental Figure S1). For comparison, thickness and density of MTs are schematically indicated by green bars. Top, enlargement of the indicated segment. (C) Schematic representation of a real trajectory of a molecule moving between microtubules in a bundle is shown in black. Yellow and black circles indicate binding events of tau with microtubules. The recorded pseudotrajectory is indicated in red. Only the binding events within the time frame (Δt) are detected and indicated by the yellow circles. (D) Time series showing the movement of a syp-mCherry–tagged vesicle in a PC12 cell process. In contrast to tau, localization of syp-mCherry over time indicates directional movement along a single MT. Scale bar, 1 μm.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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Figure 2: Tau interacts with multiple microtubules in processes of PC12 cells. (A) Schematic representation showing the geometry and MT distribution in a process of a neuronally differentiated PC12 cell. (B) Localization of a single Halo-tau molecule in a PC12 cell process over time (for a high-resolution version see Supplemental Figure S1). For comparison, thickness and density of MTs are schematically indicated by green bars. Top, enlargement of the indicated segment. (C) Schematic representation of a real trajectory of a molecule moving between microtubules in a bundle is shown in black. Yellow and black circles indicate binding events of tau with microtubules. The recorded pseudotrajectory is indicated in red. Only the binding events within the time frame (Δt) are detected and indicated by the yellow circles. (D) Time series showing the movement of a syp-mCherry–tagged vesicle in a PC12 cell process. In contrast to tau, localization of syp-mCherry over time indicates directional movement along a single MT. Scale bar, 1 μm.
Mentions: The spatial resolution of single-molecule tracking (∼20 nm) was high enough to discriminate between tau being attached to one particular MT or to its neighbor in processes of PC12 cells (Figure 2A). Note that the spacing between MTs in PC12 neurites is ∼70 nm (Jacobs and Stevens, 1986), a much higher value than the typical MT–MT distance in axons (Hirokawa and Takemura, 2005) due to the fact that PC12 cells do not develop axonal compartmentalization. Figure 2B (see also Supplemental Movie S2) documents the “pseudotrajectory” of binding events of tau over time (for a real trajectory, see Figure 2C). It is also evident that tau binds to several neighboring MTs in the transversal direction during the recording time (Figure 2B).

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