The intralumenal fragment pathway mediates ESCRT-independent surface transporter down-regulation
The intralumenal fragment pathway mediates ESCRT-independent surface transporter down-regulation
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DOI：
10.1038/s41467-018-07734-5
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发表时间：
2018-12-18
影响因子：
16.6
通讯作者：
Brett, Christopher Leonard
中科院分区：
文献类型：
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作者：
McNally, Erin Kate;Brett, Christopher Leonard
表面受体和转运蛋白下调被认为是唯一介导的经典多泡体（MVB）途径和ESCRT（内体分选复合物运输所需）。然而，已知很少有表面蛋白需要ESCRT进行下调，并且正在出现ESCRT独立降解的报告，这表明存在替代途径。在这里，使用酿酒酵母作为一个模型，我们表明，己糖转运蛋白Hxt 3不需要ESCRT下调赋予2-脱氧葡萄糖的抗性。这与GFP标记的Hxt 3绕过ESCRT介导的进入内体处的腔内囊泡一致。相反，Hxt 3-GFP在空泡溶酶体膜上积累，并被分选到一个区域，在融合后，被内化为腔内片段（ILF）并降解。此外，热应激或放线菌酮触发Hxt 3-GFP和其他表面转运蛋白（Itr 1，Aqr 1）的降解，通过这种ESCRT-独立的过程。如何ILF途径相比，MVB途径，并可能有助于生理进行了讨论。
Surface receptor and transporter protein down-regulation is assumed to be exclusively mediated by the canonical multivesicular body (MVB) pathway and ESCRTs (Endosomal Sorting Complexes Required for Transport). However, few surface proteins are known to require ESCRTs for down-regulation, and reports of ESCRT-independent degradation are emerging, suggesting that alternative pathways exist. Here, using Saccharomyces cerevisiae as a model, we show that the hexose transporter Hxt3 does not require ESCRTs for down-regulation conferring resistance to 2-deoxyglucose. This is consistent with GFP-tagged Hxt3 bypassing ESCRT-mediated entry into intralumenal vesicles at endosomes. Instead, Hxt3-GFP accumulates on vacuolar lysosome membranes and is sorted into an area that, upon fusion, is internalized as an intralumenal fragment (ILF) and degraded. Moreover, heat stress or cycloheximide trigger degradation of Hxt3-GFP and other surface transporter proteins (Itr1, Aqr1) by this ESCRT-independent process. How this ILF pathway compares to the MVB pathway and potentially contributes to physiology is discussed.