Ramnarayanan Sai Prasad, Cheng Christina A, Bastaki Maria, Tuma Pamela L
Department of Biology, The Catholic University of America, Washington, DC 20064, USA.
Mol Biol Cell. 2007 Jul;18(7):2707-15. doi: 10.1091/mbc.e07-02-0096. Epub 2007 May 9.
Unlike simple epithelial cells that directly target newly synthesized glycophosphatidylinositol (GPI)-anchored and single transmembrane domain (TMD) proteins from the trans-Golgi network to the apical membrane, hepatocytes use an indirect pathway: proteins are delivered to the basolateral domain and then selectively internalized and transcytosed to the apical plasma membrane. Myelin and lymphocyte protein (MAL) and MAL2 have been identified as regulators of direct and indirect apical delivery, respectively. Hepatocytes lack endogenous MAL consistent with the absence of direct apical targeting. Does MAL expression reroute hepatic apical residents into the direct pathway? We found that MAL expression in WIF-B cells induced the formation of cholesterol and glycosphingolipid-enriched Golgi domains that contained GPI-anchored and single TMD apical proteins; polymeric IgA receptor (pIgA-R), polytopic apical, and basolateral resident distributions were excluded. Basolateral delivery of newly synthesized apical residents was decreased in MAL-expressing cells concomitant with increased apical delivery; pIgA-R and basolateral resident delivery was unchanged. These data suggest that MAL rerouted selected hepatic apical proteins into the direct pathway.
与简单上皮细胞不同，简单上皮细胞直接将新合成的糖磷脂酰肌醇（GPI）锚定蛋白和单跨膜结构域（TMD）蛋白从反式高尔基体网络运输到顶端膜，而肝细胞则采用间接途径：蛋白质先被递送至基底外侧结构域，然后被选择性内化并经胞吞转运至顶端质膜。髓鞘和淋巴细胞蛋白（MAL）和MAL2已分别被鉴定为直接和间接顶端递送的调节因子。肝细胞缺乏内源性MAL，这与缺乏直接顶端靶向一致。MAL的表达是否会将肝脏顶端驻留蛋白重新导向直接途径？我们发现，在WIF-B细胞中表达MAL会诱导富含胆固醇和糖鞘脂的高尔基体结构域的形成，这些结构域包含GPI锚定蛋白和单TMD顶端蛋白；多聚免疫球蛋白A受体（pIgA-R）、多结构域顶端蛋白和基底外侧驻留蛋白的分布被排除在外。在表达MAL的细胞中，新合成的顶端驻留蛋白的基底外侧递送减少，同时顶端递送增加；pIgA-R和基底外侧驻留蛋白的递送没有变化。这些数据表明，MAL将选定的肝脏顶端蛋白重新导向了直接途径。
