肝细胞极性与膜蛋白分选的分子机制

Molecular Mechanisms of Hepatocyte Polarity and Membrane Protein Sorting

肝细胞是高度特化的极性上皮细胞,细胞质膜蛋白的分选和极性转运对于肝细胞极性的建立与维持至关重要.首先,膜蛋白在内质网中合成,随后经高尔基体加工修饰,再由反面高尔基体进一步分选,最后通过膜泡运输等不同的机制分别转运到胆汁腔面或窦状隙面,行使其特殊的功能.近些年来,细胞内负责转运的细胞器和主要的分选信号已逐步被揭示.特别是循环内体也被证明参与了胆汁腔面和窦状隙面膜蛋白的极性分选和转运.肝细胞的极性一旦遭到破坏,将会引起胆汁分泌障碍以及其他肝脏功能的损伤,从而可能导致肝脏糖脂代谢紊乱,甚至丧失正常的生理功能.因此,深入研究肝脏细胞极性的形成与维持机制,将为多种肝脏疾病的预防和治疗寻找到新的方向和靶点,具有重要的理论和临床实践意义.

Hepatocytes, the major epithelial cells in the liver, are highly polarized. The intracellular sorting and polarized trafficking of apical/canalicular and basolateral/sinusoidal proteins are essential to the maintenance and generation of membrane polarity in hepatocytes. Through biogenesis, a plasma membrane protein is first synthesized in the endoplasmic reticulum, modified in Golgi, and finally sorted in the trans-Golgi network （TGN）. From the TGN, they are further sorted to either the canalicular or sinusoidal membrane domains. Recently, major sorting signals and intracellular sorting compartments have been uncovered. In particular, recycling endosome has come out as a central player of hepatocytes and epithelial cells in the apical and basolateral polarized sorting. Loss of hepatic polarity leads to a number of pathogenic conditions such as bile secretory failure （cholestasis）, carbohydrate and lipid metabolism disorder, and other liver diseases. Thus, a better understanding of the maintenance and generation of membrane polarity is required for the prevention and treatment of major liver diseases.