IST1 regulates select endosomal recycling pathways.
IST1 regulates select endosomal recycling pathways.
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IST1 调节选择的内体回收途径。
DOI：
10.1101/2023.07.31.551359
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Hanson,PhyllisI
中科院分区：
文献类型：
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作者：
Clippinger,AmyK;Naismith,TeresaV;Yoo,Wonjin;Jansen,Silvia;Kast,David;Hanson,PhyllisI
ESCRT(运输所需的内体分选复合体)是一组模块化的蛋白质复合体，具有膜重塑活动，包括形成和释放腔内小泡(ILV)以产生多囊内体。虽然已知12个ESCRT-III蛋白中的大多数在ILV的形成中发挥作用，但IST1与更广泛的内体重构事件有关。在这里，我们扩展了先前关于IST1在内体运输中的功能的研究，并确定IST1与其结合伙伴CHMP1B一起有助于早期内体携带者的断裂。从功能上讲，耗尽IST1会损害转铁蛋白受体从早期/分选的内吞体向内吞循环室的输送，而是增加其通过富含网状蛋白适配器AP-1的外周内体向质膜的快速再循环。IST1对于甘露糖6-磷酸受体从早期/分选内体中的出口也是重要的。对这些内体上的IST1结合伙伴的检查表明，IST1既与CHMP1B相互作用，也与先前报道的含有MIT结构域的分选Nexin SNX15相互作用，以调节内体循环。动力学和空间分析表明，SNX15和IST1占据了一个不同于以前与货物回收或降解相关的含有笼状蛋白的亚区。利用活细胞显微镜，我们证明了SNX15和CHMP1B交替控制IST1在内体周长和内体小管底部的这个结构域的募集。这些发现表明，IST1在早期/分选内体的特定循环途径中发挥着重要的调节作用。
ESCRTs (Endosomal Sorting Complex Required for Transport) are a modular set of protein complexes with membrane remodeling activities that include the formation and release of intralumenal vesicles (ILVs) to generate multivesicular endosomes. While most of the 12 ESCRT-III proteins are known to play roles in ILV formation, IST1 has been associated with a wider range of endosomal remodeling events. Here, we extend previous studies of IST1 function in endosomal trafficking and establish that IST1, along with its binding partner CHMP1B, contributes to scission of early endosomal carriers. Functionally, depleting IST1 impairs delivery of transferrin receptor from early/sorting endosomes to the endocytic recycling compartment and instead increases its rapid recycling to the plasma membrane via peripheral endosomes enriched in the clathrin adaptor AP-1. IST1 is also important for export of mannose 6-phosphate receptor from early/sorting endosomes. Examination of IST1 binding partners on these endosomes revealed that IST1 interacts both with CHMP1B and with the MIT domain-containing sorting nexin SNX15 previously reported to regulate endosomal recycling. Kinetic and spatial analyses showed that SNX15 and IST1 occupy a clathrin-containing subdomain distinct from those previously connected to cargo retrieval or degradation. Using live-cell microscopy we demonstrate that SNX15 and CHMP1B alternately control recruitment of IST1 to this domain on the endosomal perimeter and the base of endosomal tubules. These findings indicate that IST1 plays an important and regulated role in specific recycling pathways from the early/sorting endosome.