Saric Amra, Freeman Spencer A
Neurosciences and Cellular and Structural Biology Division, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, United States.
Program in Cell Biology, Peter Gilgan Center for Research and Learning, Hospital for Sick Children, Toronto, ON, Canada.
Front Cell Dev Biol. 2021 Jan 8;8:611326. doi: 10.3389/fcell.2020.611326. eCollection 2020.
Eukaryotic cells employ diverse uptake mechanisms depending on their specialized functions. While such mechanisms vary widely in their defining criteria: scale, molecular machinery utilized, cargo selection, and cargo destination, to name a few, they all result in the internalization of extracellular solutes and fluid into membrane-bound endosomes. Upon scission from the plasma membrane, this compartment is immediately subjected to extensive remodeling which involves tubulation and vesiculation/budding of the limiting endomembrane. This is followed by a maturation process involving concomitant retrograde transport by microtubule-based motors and graded fusion with late endosomes and lysosomes, organelles that support the degradation of the internalized content. Here we review an important determinant for sorting and trafficking in early endosomes and in lysosomes; the control of tension on the endomembrane. Remodeling of endomembranes is opposed by high tension (caused by high hydrostatic pressure) and supported by the relief of tension. We describe how the timely and coordinated efflux of major solutes along the endocytic pathway affords the cell control over such tension. The channels and transporters that expel the smallest components of the ingested medium from the early endocytic fluid are described in detail as these systems are thought to enable endomembrane deformation by curvature-sensing/generating coat proteins. We also review similar considerations for the lysosome where resident hydrolases liberate building blocks from luminal macromolecules and transporters flux these organic solutes to orchestrate trafficking events. How the cell directs organellar trafficking based on the luminal contents of organelles of the endocytic pathway is not well-understood, however, we propose that the control over membrane tension by solute transport constitutes one means for this to ensue.
真核细胞根据其特定功能采用多种摄取机制。虽然这些机制在其定义标准方面差异很大：规模、所利用的分子机制、货物选择和货物目的地等等，但它们都导致细胞外溶质和液体内化到膜结合的内体中。从质膜分裂后，这个区室立即经历广泛的重塑，这涉及到限制内膜的微管形成和囊泡化/出芽。随后是一个成熟过程，涉及基于微管的马达伴随的逆行运输以及与晚期内体和溶酶体的分级融合，这些细胞器支持内化内容物的降解。在这里，我们综述了早期内体和溶酶体中分拣和运输的一个重要决定因素；内膜张力的控制。内膜的重塑受到高张力（由高静水压力引起）的阻碍，并因张力的缓解而得到支持。我们描述了主要溶质沿着内吞途径的及时和协调流出如何使细胞能够控制这种张力。详细描述了从早期内吞液中排出摄入介质最小成分的通道和转运体，因为这些系统被认为能够通过曲率感知/产生包被蛋白来实现内膜变形。我们还综述了溶酶体的类似考虑因素，其中驻留水解酶从腔内大分子中释放构建块，转运体使这些有机溶质流动以协调运输事件。然而，细胞如何根据内吞途径细胞器的腔内内容物来指导细胞器运输尚不清楚，我们提出溶质运输对膜张力的控制构成了实现这一点的一种方式。
