肝细胞生成素——一种非经典分泌蛋白

肝细胞生成素(hepatopoietin ,HPO)是一种分泌蛋白.为了研究肝细胞生成素的分泌途径,利用SignalP软件分析了HPO的氨基酸序列,但HPO序列中没有经典分泌蛋白的信号肽.Western印迹实验证明,HPO能以双体形式从细胞中分泌出来.特异性体外阻断实验表明,布雷菲尔德菌素A(brefeldinA)和莫能菌素(monensin)都不能阻断HPO的分泌,说明HPO并不通过经典的内质网 高尔基体(ER -Golgi)途径分泌;优降糖(glyburide)对HPO的分泌没有抑制作用,说明HPO的分泌并不是由ABC1(ATP bindingcassette)转运子介导的;DNP和NH4Cl也不能刺激HPO的分泌,说明内体 溶酶体系统不参与HPO的分泌.上述结果表明,HPO是一种非经典分泌蛋白(non classicalsecretoryprotein) ,能以双体形式从细胞中分泌出来.但和已知的非经典分泌蛋白IL -1β不同,HPO的分泌并不是通过ABC1转运子介导的,内体 溶酶体系统也不参与其分泌.

Hepatopoietin--A Non-classical Secretory Protein

Hepatopoietin (HPO) could be secreted by the cultured hepatocytes.Unlike classical secretory proteins, HPO lacks a typical signal sequence which allows the transfer of the protein across the membrane of endoplastic reticulum(ER). Western blot analysis indicated that HPO was secreted by the hepatoma cells as a dimmer. Brefeldin A and monensin did not inhibit the secretion of HPO. This demonstrated that the secretion of HPO did not follow the ER-Golgi patheway. Glyburide could block the secretion of non-classical secretory protein IL-1β through ABC1 transporter pathway,but did not inhibit the secretion of HPO from hepatoma cells. This suggested that the ABC1 transporter was not involved in the secretion of HPO. On the other hand, DNP and NH-4Cl did not increase the secretion of HPO either.This meant that endosome and lysosome-related vesicles were not concerned with the secretion of HPO. Taken together, it can be concluded that HPO was a non-classical secretory protein released through a novel secretory pathway.