Endocytic sorting and recycling require membrane phosphatidylserine asymmetry maintained by TAT-1/CHAT-1.
Endocytic sorting and recycling require membrane phosphatidylserine asymmetry maintained by TAT-1/CHAT-1.
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DOI：
10.1371/journal.pgen.1001235
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发表时间：
2010-12-09
期刊：
影响因子：
4.5
通讯作者：
Wang X
中科院分区：
文献类型：
--
作者：
Chen B;Jiang Y;Zeng S;Yan J;Li X;Zhang Y;Zou W;Wang X
内吞分选是通过在早期内体中形成形态和功能上不同的亚结构域来实现的。用于回收的货物被分类并通过新形成的管状膜运输，但调节膜管化的过程却知之甚少。在这里，我们发现了一个新的秀丽隐杆线虫Cdc50家族蛋白CHAT-1，它作为TAT-1 p4 - atp酶的伴侣，调节膜磷脂酰丝氨酸（PS）不对称和内噬运输。在chat-1和tat-1突变体中，内噬分选过程被破坏，导致货物回收和降解缺陷。TAT-1和CHAT-1共定位于早期核内体的管状结构域、管状内噬循环室（ERC）和循环核内体，其中PS在细胞质表面富集。tat-1和chat-1功能的缺失破坏了膜PS的不对称性，破坏了管状膜结构。我们的数据表明，CHAT-1和TAT-1维持膜磷脂酰丝氨酸的不对称性，从而促进膜管化，调节内吞噬分选和再循环。细胞从细胞外环境中吸收营养物质和其他大分子的过程被称为内吞作用。在细胞表面，外部分子被包裹在称为核内体的膜球中。早期核内体充当分选站，将内容物（货物分子）引导到细胞内正确的隔室。这被认为是通过形成具有不同形状和功能的膜结构来实现的。例如，用于回收和降解的货物分别通过管状膜结构和大泡状隔室进行处理。然而，人们对早期核内体膜如何形成不同的结构知之甚少。在这里，我们发现两个蛋白，CHAT-1和TAT-1，调节膜结构，并在线虫正常的内吞运输中起重要作用。TAT-1和CHAT-1存在于沿着分选和再循环途径的管状膜结构中，在那里它们用一种称为磷脂酰丝氨酸（PS）的脂质丰富外膜层，并可能改变膜曲率。tat-1和chat-1功能的丧失破坏了PS的不对称分布，取消了管状膜结构，并取消了内吞噬分类/再循环。我们的数据支持TAT-1/ chat -1调节的膜PS不对称在促进内吞货物分类和回收的膜管中的作用。
Endocytic sorting is achieved through the formation of morphologically and functionally distinct sub-domains within early endosomes. Cargoes destined for recycling are sorted to and transported through newly-formed tubular membranes, but the processes that regulate membrane tubulation are poorly understood. Here, we identified a novel Caenorhabditis elegans Cdc50 family protein, CHAT-1, which acts as the chaperone of the TAT-1 P4-ATPase to regulate membrane phosphatidylserine (PS) asymmetry and endocytic transport. In chat-1 and tat-1 mutants, the endocytic sorting process is disrupted, leading to defects in both cargo recycling and degradation. TAT-1 and CHAT-1 colocalize to the tubular domain of the early endosome, the tubular endocytic recycling compartment (ERC), and the recycling endosome where PS is enriched on the cytosolic surface. Loss of tat-1 and chat-1 function disrupts membrane PS asymmetry and abrogates the tubular membrane structure. Our data suggest that CHAT-1 and TAT-1 maintain membrane phosphatidylserine asymmetry, thus promoting membrane tubulation and regulating endocytic sorting and recycling. The process by which cells take up nutrients and other large molecules from the extracellular environment is known as endocytosis. At the cell surface, external molecules become enclosed in membrane spheres called endosomes. Early endosomes serve as a sorting station, directing the contents (cargo molecules) to the correct compartment within the cell. This is thought to be achieved by the formation of membrane structures with distinct shape and function. For example, cargoes destined for recycling and degradation are processed through tubular membrane structures and big vesicular compartments, respectively. However, it is poorly understood how early endosome membranes are shaped into different structures. Here we show that two proteins, CHAT-1 and TAT-1, regulate membrane structure and are important for normal endocytic transport in the nematode worm C. elegans. TAT-1 and CHAT-1 are found in tubular membrane structures along the sorting and recycling pathway, where they enrich the outer membrane layer with a lipid called phosphatidylserine (PS) and probably change the membrane curvature. Loss of tat-1 and chat-1 function disrupts the asymmetric distribution of PS, abolishes tubular membrane structures, and abrogates endocytic sorting/recycling. Our data support a role of TAT-1/CHAT-1–regulated membrane PS asymmetry in promoting membrane tubulation for endocytic cargo sorting and recycling.
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