Department of Cell Biology, Duke University, Durham, NC, USA.
FEBS J. 2022 Feb;289(3):659-670. doi: 10.1111/febs.15882. Epub 2021 Apr 28.
Polarized epithelial cells are characterized by the asymmetric distribution of proteins between apical and basolateral domains of the plasma membrane. This asymmetry is highly conserved and is fundamental to epithelial cell physiology, development, and homeostasis. How proteins are segregated for apical or basolateral delivery, a process known as sorting, has been the subject of considerable investigation for decades. Despite these efforts, the rules guiding apical sorting are poorly understood and remain controversial. Here, we consider mechanisms of apical membrane protein sorting and argue that they are largely driven by self-organization and biophysical principles. The preponderance of data to date is consistent with the idea that apical sorting is not ruled by a dedicated protein-based sorting machinery and relies instead on the concerted effects of oligomerization, phase separation of lipids and proteins in membranes, and pH-dependent glycan interactions.
极化的上皮细胞的特征是蛋白质在质膜的顶侧和基底外侧区域之间的不对称分布。这种不对称性高度保守，是上皮细胞生理学、发育和体内平衡的基础。几十年来，蛋白质如何被分选到顶侧或基底外侧进行运输（这个过程称为分拣）一直是大量研究的主题。尽管进行了这些努力，但指导顶部分选的规则仍知之甚少，并且仍存在争议。在这里，我们考虑了顶端膜蛋白分拣的机制，并认为这些机制主要是由自组织和物理化学原理驱动的。迄今为止，大多数数据都支持这样一种观点，即顶部分选不是由专门的基于蛋白质的分拣机制决定的，而是依赖于寡聚化、膜中脂质和蛋白质的相分离以及 pH 依赖性聚糖相互作用的协同效应。
