p25 of the dynactin complex plays a dual role in cargo binding and dynactin regulation

The Journal of Biological Chemistry
Rongde QiuXin Xiang

Abstract

Cytoplasmic dynein binds its cargoes via the dynactin complex and cargo adapters, and the dynactin pointed-end protein p25 is required for dynein-dynactin binding to the early endosomal dynein adapter HookA (Hook in the fungus Aspergillus nidulans). However, it is unclear whether the HookA-dynein-dynactin interaction requires p27, another pointed-end protein forming heterodimers with p25 within vertebrate dynactin. Here, live-cell imaging and biochemical pulldown experiments revealed that although p27 is a component of the dynactin complex in A. nidulans, it is dispensable for dynein-dynactin to interact with ΔC-HookA (cytosolic HookA lacking its early endosome-binding C terminus) and is not critical for dynein-mediated early endosome transport. Using mutagenesis, imaging, and biochemical approaches, we found that several p25 regions are required for the ΔC-HookA-dynein-dynactin interaction, with the N terminus and loop1 being the most critical regions. Interestingly, p25 was also important for the microtubule (MT) plus-end accumulation of dynactin. This p25 function in dynactin localization also involved p25's N terminus and the loop1 critical for the ΔC-HookA-dynein-dynactin interaction. Given that dynactin's MT plus-end loca...Continue Reading

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Citations

Apr 9, 2020·Molecular Biology of the Cell·Rongde QiuXin Xiang
Apr 3, 2020·Molecular Biology of the Cell·Kei SaitoYoko Y Toyoshima
Mar 17, 2019·Journal of Cell Science·Mara A Olenick, Erika L F Holzbaur
Nov 17, 2020·Frontiers in Cell and Developmental Biology·Xin Xiang, Rongde Qiu
Mar 19, 2021·The EMBO Journal·Clinton K LauAndrew P Carter
May 21, 2021·The Journal of Cell Biology·Sydney E CasonErika L F Holzbaur
Aug 10, 2021·Neurobiology of Aging·Md Golam SharoarRiqiang Yan

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