Clathrin-independent endocytosis (CIE) mediates the cellular uptake of many extracellular ligands, receptors, and pathogens, including several life-threatening bacterial toxins and viruses. So far, our understanding of CIE carrier formation has lagged behind that of clathrin-coated vesicles. Impediments have been the imprecise definition of some CIE pathways, the lack of specific cargoes being transported and of exclusive cytosolic markers and regulators. Notwithstanding these limitations, three distinct molecular mechanisms by which CIE carriers form can be defined. Cargo capture by cytosolic proteins is the main mechanism used by fast endophilin-mediated endocytosis (FEME) and interleukin 2 receptor (IL-2R) endocytosis. Acute signaling-induced membrane remodeling drives macropinocytosis. Finally, extracellular lipid or cargo clustering by the glycolipid-lectin (GL-Lect) hypothesis mediates the uptake of Shiga and cholera toxins and receptors by the CLIC/GEEC pathway. Here, we review these mechanisms and highlight current gaps in knowledge that will need to be addressed to complete our understanding of CIE.

不依赖网格蛋白的内吞作用（CIE）介导许多细胞外配体，受体和病原体的细胞摄取，包括几种威胁生命的细菌毒素和病毒。到目前为止，我们对CIE载体形成的理解落后于网格蛋白包被的囊泡。障碍是某些CIE途径的定义不精确，缺乏特定的货物运输以及缺乏胞浆标志物和调节剂。尽管有这些限制，仍可以定义形成CIE载体的三种不同的分子机制。胞质蛋白捕获货物是快速内啡肽介导的内吞作用（FEME）和白介素2受体（IL-2R）内吞作用的主要机制。急性信号诱导的膜重塑驱动巨胞饮作用。最后，糖脂-凝集素（GL-Lect）假说在细胞外脂质或货物聚集中通过CLIC / GEEC途径介导了志贺氏菌和霍乱毒素及受体的摄取。在这里，我们回顾了这些机制，并强调了当前需要弥补的知识差距，以完成我们对CIE的理解。