Cargo Release from Myosin V Requires the Convergence of Parallel Pathways that Phosphorylate and Ubiquitylate the Cargo Adaptor.
Cargo Release from Myosin V Requires the Convergence of Parallel Pathways that Phosphorylate and Ubiquitylate the Cargo Adaptor.
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肌球蛋白V的货物释放需要将货物衔接子磷酸化和泛素化的平行途径的会聚。
DOI：
10.1016/j.cub.2020.08.062
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发表时间：
2020-11-16
期刊：
影响因子：
--
通讯作者：
Weisman LS
中科院分区：
文献类型：
--
作者：
Wong S;Hepowit NL;Port SA;Yau RG;Peng Y;Azad N;Habib A;Harpaz N;Schuldiner M;Hughson FM;MacGurn JA;Weisman LS
细胞功能需要分子马达将货物运输到正确的细胞内位置。电机适配器复合体的受监管组装和拆卸可确保货物在始发地装载并在目的地卸载。在酿酒酵母中，在细胞周期的早期，一部分液泡被运输到新芽中。这种运输需要肌球蛋白 V 马达 Myo2，它通过液泡特异性接头蛋白 Vac17 附着在液泡上。 Vac17 还与液泡膜蛋白 Vac8 结合。一旦液泡通过 Myo2-Vac17-Vac8 复合物进入芽皮层，Vac17 就会降解，液泡从 Myo2 中释放出来。然而，控制 Myo2-Vac17-Vac8 复合物解离的机制尚不清楚。芽皮层 Vac17 接头的泛素化提供了液泡释放的空间调节。在这里，我们报告仅泛素化不足以释放货物。我们发现从液泡开始的平行途径与泛素化汇合，从 Myo2 中释放液泡。具体来说，我们表明，无论 Yck3 和 Vps41 在 HOPS 介导的囊泡束缚中的已知作用如何，Yck3 和 Vps41 都是 Vac17 在其 Myo2 结合域中磷酸化所必需的。这些磷酸化事件使得泛素化的 Vac17 从 Myo2 和 Vac8 中释放出来。我们的数据表明，Vps41 通过 Yck3（一种酪蛋白激酶 I，也可能是另一种未知激酶）调节 Vac17 的磷酸化。从 Myo2 释放液泡需要平行途径，这表明整合多个信号来终止细胞器遗传。递送后，货物通过需要接头蛋白泛素化的途径与其分子马达解偶联。在这里，黄等人。发现这还不够，第二条平行通路也作用于适配器。他们表明，从肌球蛋白 V 马达释放液泡货物需要两条途径的汇聚。
Cellular function requires molecular motors to transport cargoes to their correct intracellular locations. The regulated assembly and disassembly of motor-adaptor complexes ensures that cargoes are loaded at their origin and unloaded at their destination. In Saccharomyces cerevisiae, early in the cell cycle, a portion of the vacuole is transported into the emerging bud. This transport requires a myosin V motor, Myo2, which attaches to the vacuole via Vac17, the vacuole specific adaptor protein. Vac17 also binds to Vac8, a vacuolar membrane protein. Once the vacuole is brought to the bud cortex via the Myo2-Vac17-Vac8 complex, Vac17, is degraded and the vacuole is released from Myo2. However, mechanisms governing dissociation of the Myo2-Vac17-Vac8 complex are not well understood. Ubiquitylation of the Vac17 adaptor at the bud cortex provides spatial regulation of vacuole release. Here, we report that ubiquitylation alone is not sufficient for cargo release. We find that a parallel pathway, which initiates on the vacuole, converges with ubiquitylation to release the vacuole from Myo2. Specifically, we show that Yck3 and Vps41, independent of their known roles in HOPS-mediated vesicle tethering, are required for the phosphorylation of Vac17 in its Myo2 binding domain. These phosphorylation events allow ubiquitylated Vac17 to be released from Myo2 and Vac8. Our data suggest that Vps41 is regulating the phosphorylation of Vac17 via Yck3, a casein kinase I, and likely another unknown kinase. That parallel pathways are required to release the vacuole from Myo2 suggests that multiple signals are integrated to terminate organelle inheritance. After delivery, cargo is uncoupled from its molecular motor via a pathway that requires ubiquitylation of the adaptor protein. Here, Wong et al. discover that this is not sufficient, and a second, parallel pathway also acts on the adaptor. They show that convergence of both pathways is required to release the vacuole cargo from the myosin V motor.
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DOI：
10.1083/jcb.201201024
发表时间：
2012-07-09
期刊：
The Journal of cell biology
影响因子：
--
作者：
Eves PT;Jin Y;Brunner M;Weisman LS
通讯作者：
Weisman LS
影响因子：
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影响因子：
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