On and off controls within dynein-dynactin on native cargoes

The dynein-dynactin nanomachine transports cargoes along microtubules in cells. Why dynactin interacts separately with the dynein motor and also with microtubules is hotly debated. Here we disrupted these interactions in a targeted manner on phagosomes extracted from cells, followed by optical trapping to interrogate native dynein- dynactin teams on single phagosomes. Perturbing the dynactin- dynein interaction reduced dynein's on rate to microtubules. In contrast, perturbing the dynactin-microtubule interaction increased dynein's off rate markedly when dynein was generating force against the optical trap. The dynactin-microtubule link is therefore required for persistence against load, a finding of importance because diseaserelevant mutations in dynein-dynactin are known to interfere with high-load functions of dynein in cells. Our findings call attention to a less studied property of dynein-dynactin, namely, its detachment against load, in understanding dynein dysfunction.

Automated summary

Disrupting the interactions between dynactin and dynein or microtubules impacts dynein's behavior on microtubules and its ability to generate force. The dynactin-microtubule link is shown to be crucial for dynein's persistence against load, shedding light on dynein dysfunction.