State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.
University of Chinese Academy of Sciences, Beijing, China.
Nat Cell Biol. 2024 Oct;26(10):1652-1668. doi: 10.1038/s41556-024-01499-4. Epub 2024 Sep 19.
Endocytosis and recycling control the uptake and retrieval of various materials, including membrane proteins and lipids, in all eukaryotic cells. These processes are crucial for cell growth, organization, function and environmental communication. However, the mechanisms underlying efficient, fast endocytic recycling remain poorly understood. Here, by utilizing a biosensor and imaging-based screening, we uncover a recycling mechanism that couples endocytosis and fast recycling, which we name the clathrin-associated fast endosomal recycling pathway (CARP). Clathrin-associated tubulovesicular carriers containing clathrin, AP1, Arf1, Rab1 and Rab11, while lacking the multimeric retrieval complexes, are generated at subdomains of early endosomes and then transported along actin to cell surfaces. Unexpectedly, the clathrin-associated recycling carriers undergo partial fusion with the plasma membrane. Subsequently, they are released from the membrane by dynamin and re-enter cells. Multiple receptors utilize and modulate CARP for fast recycling following endocytosis. Thus, CARP represents a previously unrecognized endocytic recycling mechanism with kiss-and-run membrane fusion.
内吞作用和回收控制着各种物质的摄取和回收，包括膜蛋白和脂质，在所有真核细胞中。这些过程对于细胞的生长、组织、功能和环境通讯至关重要。然而，有效的、快速的内吞体回收的机制仍知之甚少。在这里，我们通过利用生物传感器和基于成像的筛选，揭示了一种将内吞作用和快速回收偶联的回收机制，我们将其命名为网格蛋白相关的快速内体回收途径 (CARP)。网格蛋白相关的管状囊泡载体包含网格蛋白、AP1、Arf1、Rab1 和 Rab11，而缺少多聚体回收复合物，在早期内体的亚域中产生，然后沿着肌动蛋白运输到细胞表面。出乎意料的是，网格蛋白相关的回收载体与质膜发生部分融合。随后，它们被 dynamin 从膜上释放出来并重新进入细胞。多种受体在内吞作用后利用和调节 CARP 进行快速回收。因此，CARP 代表了一种以前未被识别的具有亲吻-跑膜融合的内吞体回收机制。
