Life Sciences Institute, University of Michigan, Ann Arbor, MI, USA.
Cellular and Molecular Biology Graduate Program, University of Michigan, Ann Arbor, MI, USA.
Curr Genet. 2021 Dec;67(6):865-869. doi: 10.1007/s00294-021-01195-y. Epub 2021 Jun 10.
A major question in cell biology is, how are organelles and macromolecular machines moved within a cell? The delivery of cargoes to the right place at the right time within a cell is critical to cellular health. Failure to do so is often catastrophic for animal physiology and results in diseases of the gut, brain, and skin. In budding yeast, a myosin V motor, Myo2, moves cellular materials from the mother cell into the growing daughter bud. Myo2-based transport ensures that cellular contents are shared during cell division. During transport, Myo2 is often linked to its cargo via cargo-specific adaptor proteins. This simple organism thus serves as a powerful tool to study how myosin V moves cargo, such as organelles. Some critical questions include how myosin V moves along the actin cytoskeleton, or how myosin V attaches to cargo in the mother. Other critical questions include how the cargo is released from myosin V when it reaches its final destination in the bud. Here, we review the mechanisms that regulate the vacuole-specific adaptor protein, Vac17, to ensure that Myo2 delivers the vacuole to the bud and releases it at the right place and the right time. Recent studies have revealed that Vac17 is regulated by ubiquitylation and phosphorylation events that coordinate its degradation and the detachment of the vacuole from Myo2. Thus, multiple post-translational modifications tightly coordinate cargo delivery with cellular events. It is tempting to speculate that similar mechanisms regulate other cargoes and molecular motors.
细胞生物学的一个主要问题是，细胞器和大分子机器如何在细胞内移动？在细胞内将货物按时运送到正确的位置对于细胞健康至关重要。如果不能做到这一点，动物的生理机能通常会受到灾难性的影响，并导致肠道、大脑和皮肤疾病。在出芽酵母中，肌球蛋白 V 马达 Myo2 将细胞物质从母细胞运送到正在生长的子芽中。基于 Myo2 的运输确保了细胞分裂过程中细胞内容物的共享。在运输过程中，Myo2 通常通过货物特异性衔接蛋白与货物相连。因此，这个简单的生物体是研究肌球蛋白 V 如何移动货物（如细胞器）的有力工具。一些关键问题包括肌球蛋白 V 如何沿着肌动蛋白细胞骨架移动，或者肌球蛋白 V 如何在母细胞中附着于货物。其他关键问题包括当货物到达子芽的最终目的地时，如何从肌球蛋白 V 上释放货物。在这里，我们回顾了调节液泡特异性衔接蛋白 Vac17 的机制，以确保 Myo2 将液泡运送到子芽并在适当的时间和地点释放它。最近的研究表明，Vac17 通过泛素化和磷酸化事件进行调节，这些事件协调了 Vac17 的降解和液泡与 Myo2 的分离。因此，多个翻译后修饰紧密协调货物的输送与细胞事件。人们不禁要推测，类似的机制是否调节其他货物和分子马达。
