Li Ming, Koshi Tatsuhiro, Emr Scott D
Weill Institute for Cell and Molecular Biology and Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853.
Weill Institute for Cell and Molecular Biology and Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853
J Cell Biol. 2015 Nov 9;211(3):639-52. doi: 10.1083/jcb.201505062. Epub 2015 Nov 2.
Cells must regulate the abundance and activity of numerous nutrient transporters in different organelle membranes to achieve nutrient homeostasis. As the recycling center and major storage organelle, lysosomes are essential for maintaining nutrient homeostasis. However, very little is known about mechanisms that govern the regulation of its membrane proteins. In this study, we demonstrated that changes of Zn(2+) levels trigger the downregulation of vacuolar Zn(2+) transporters. Low Zn(2+) levels cause the degradation of the influx transporter Cot1, whereas high Zn(2+) levels trigger the degradation of the efflux channel Zrt3. The degradation process depends on the vacuole membrane recycling and degradation pathway. Unexpectedly, we identified a RING domain-containing E3 ligase Tul1 and its interacting proteins in the Dsc complex that are important for the ubiquitination of Cot1 and partial ubiquitination of Zrt3. Our study demonstrated that the Dsc complex can function at the vacuole to regulate the composition and lifetime of vacuolar membrane proteins.
细胞必须调节不同细胞器膜中众多营养转运蛋白的丰度和活性，以实现营养稳态。作为循环中心和主要的储存细胞器，溶酶体对于维持营养稳态至关重要。然而，对于调控其膜蛋白的机制却知之甚少。在本研究中，我们证明锌离子（Zn(2+)）水平的变化会触发液泡锌离子转运蛋白的下调。低锌离子水平会导致流入转运蛋白Cot1的降解，而高锌离子水平则会触发流出通道Zrt3的降解。降解过程依赖于液泡膜循环和降解途径。出乎意料的是，我们在Dsc复合物中鉴定出一个含RING结构域的E3连接酶Tul1及其相互作用蛋白，它们对于Cot1的泛素化和Zrt3的部分泛素化很重要。我们的研究表明，Dsc复合物可在液泡发挥作用，调节液泡膜蛋白的组成和寿命。
