Fig. 3: TauC3 slows down the microtubule-dependent transport of mitochondria and reduces the processivity of APP-vesicle transport. | Molecular Psychiatry

Fig. 3: TauC3 slows down the microtubule-dependent transport of mitochondria and reduces the processivity of APP-vesicle transport.

From: Caspase-cleaved tau is senescence-associated and induces a toxic gain of function by putting a brake on axonal transport

Fig. 3

A Micrograph of a PC12 cell expressing eGFP-SDHD for tracking the movement of mitochondria in living cells. mCherry-tagged Tau or TauC3 was co-expressed by lentiviral (LV) expression. A moving mitochondrion is indicated by an arrow in the enlarged time-lapse images shown below. Scale bar, 10 µm (top) and 2 µm (bottom). B Bar graphs showing fractions of stationary and mobile mitochondria in the process. Velocity and speed of the mobile mitochondria are displayed in the middle and right graphs. Mean ± SEM, n = 12 cells with 672 trajectories (mCherry-Tau) and n = 22 cells with 1137 trajectories (mCherry-TauC3). C APP-vesicle tracking in a process of a PC12 cell using eGFP-tagged APP and an autoregressive motion algorithm. mCherry-tagged Tau or TauC3 was co-expressed by lentiviral (LV) expression. The images on the left show an overview of a cell that co-expresses tau and APP. The images on the right show selected points in time of the APP-vesicle movement from the part of the process that is indicated by the white box in the overview image. Arrows point to a moving (white) and a stationary vesicle (red). Scale bars, 10 µm (overview) and 2.5 µm (time lapse). D The quantification of the transport parameters is shown on the left. The bar chart shows fractions of mobile and stationary vesicles in the process. The velocity, processivity, and speed of the mobile vesicles are shown in the scatter plots on the right. Each point represents an average value for a respective cell (mean ± SEM of n = 21 cells with 470 trajectories (Tau) and n = 20 cells with 413 trajectories (TauC3)). E The definition of state changes of individual vesicle tracts is shown on the left. The box plot on the right shows the cumulative changes in state. Every dot represents one cell of the data set shown in D. The two diagrams in the middle show the phases of movement of 5 long representative trajectories for cells expressing Tau or TauC3. All transduced tau constructs are based on the human tau sequence. Statistically significant differences determined by unpaired Student’s t test are indicated. *p < 0.05; **p < 0.01.

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