Department of Bioengineering, McGill University, Montreal, QC H3A 0E9, Canada.
Department of Bioengineering, McGill University, Montreal, QC H3A 0E9, Canada; Department of Biomedical Engineering and Health, Episen, Université Paris-Est Créteil, 94010 Créteil Cedex, France.
Cell Rep. 2024 Aug 27;43(8):114649. doi: 10.1016/j.celrep.2024.114649. Epub 2024 Aug 18.
Each cargo in a cell employs a unique set of motor proteins for its transport. To dissect the roles of each type of motor, we developed optogenetic inhibitors of endogenous kinesin-1, -2, -3 and dynein motors and examined their effect on the transport of early endosomes, late endosomes, and lysosomes. While kinesin-1, -3, and dynein transport vesicles at all stages of endocytosis, kinesin-2 primarily drives late endosomes and lysosomes. Transient optogenetic inhibition of kinesin-1 or dynein causes both early and late endosomes to move more processively by relieving competition with opposing motors. Kinesin-2 and -3 support long-range transport, and optogenetic inhibition reduces the distances that their cargoes move. These results suggest that the directionality of transport is controlled through regulating kinesin-1 and dynein activity. On vesicles transported by several kinesin and dynein motors, modulating the activity of a single type of motor on the cargo is sufficient to direct motility.
每个细胞中的货物都使用一组独特的马达蛋白进行运输。为了剖析每种马达的作用，我们开发了光遗传学抑制剂来抑制内源性驱动蛋白-1、-2、-3 和动力蛋白，然后观察它们对早期内体、晚期内体和溶酶体运输的影响。虽然驱动蛋白-1、-3 和动力蛋白可运输胞吞作用的各个阶段的囊泡，但驱动蛋白-2 主要驱动晚期内体和溶酶体。光遗传学瞬时抑制驱动蛋白-1 或动力蛋白会通过缓解与对向马达的竞争，使早期和晚期内体更有效地进行定向运动。驱动蛋白-2 和 -3 支持长距离运输，光遗传学抑制会减少它们的货物移动的距离。这些结果表明，运输的方向性是通过调节驱动蛋白-1 和动力蛋白的活性来控制的。在几种驱动蛋白和动力蛋白运输的囊泡上，调节货物上的一种马达的活性足以引导运动。
