Figure 1.
Tau expression inhibits anterograde transport of organelles and vesicles but not of tau itself. a, Diagram of tau441, the longest isoform in human CNS, with repeat domain (R1–R4), the flanking proline-rich regions (which together constitute the microtubule-binding domain), and the N-terminal projection domain (alternatively spliced inserts in black). Phosphorylation sites in the repeat domain that control MT binding are indicated. b–f, Cortical neurons 20 h after transfection with CFP-hTau40. CFP-hTau40 is shown in blue (b); mitochondria are labeled with MitoTracker Red (c). In the overlay (d), two neurites are boxed in green (left box, with tau expression; right, without tau). The movements of mitochondria during a 1000 s period are visualized in kymographs derived from the boxed neurites with Tau expression (e) or without (f). The anterograde direction is indicated by an arrow from left to right (“ant”). g–i, Cortical neurons expressing CFP-hTau40 for 21 h. CFP-hTau40 is pseudocolored in blue (g), and mitochondria are pseudocolored in red (h). In the overlay, mitochondria are visible in the axon without tau expression but not in the axon with tau (i). j, k, Quantitation of tau distribution along an axon (same as in g; highlighted by dotted line) shown by a color gradient (j) and plotted versus axon length (k; plot extends between positions marked by diamond and arrowhead). Note that the highest apparent level is in the cell body (red, blue edges) and extends into the axon (blue, proximal; green, distal). Occasional shifts in intensity (e.g., around L = 280 μm) are caused by stronger background intensity in this area. Scale bars, 20 μm.