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bioRxiv · 10.1101/2022.06.10.495679

Tau inhibits the long-range, dynein-mediated motility of early phagosomes

Beaudet, D.·Berger, C. L.·Hendricks, A. G.
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Abstract

The misregulation of tau, a neuronal microtubule-associated protein, is linked to defective axonal transport and neurodegenerative disease. We reconstituted the motility of isolated phagosomes along microtubules to ask how the sets of motors transporting a cargo determine its motility and response to tau. Using quantitative photobleaching, we find that early phagosomes (EPs) and late phagosomes (LPs) are associated with different sets of kinesin-1, -2, -3, and dynein. While EPs exhibit unidirectional retrograde transport, LPs move bidirectionally. Previously, we found that tau biases LP transport towards the microtubule minus-end. Here, we find that tau strongly inhibits long-range retrograde EP motility. Tau impedes the forces generated by multi-dynein teams and accelerates dynein unbinding under load. Thus, specific cargoes differentially respond to tau, where dynein-complexes on EPs are more sensitive to tau than those on LPs.

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Beaudet, D., Berger, C. L., Hendricks, A. G.. 2022-06-10. Tau inhibits the long-range, dynein-mediated motility of early phagosomes. https://doi.org/10.1101/2022.06.10.495679

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