Exogenous MAL reroutes selected hepatic apical proteins into the direct pathway in WIF-B cells
Exogenous MAL reroutes selected hepatic apical proteins into the direct pathway in WIF-B cells
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DOI：
10.1091/mbc.e07-02-0096
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发表时间：
2007-07-01
影响因子：
3.3
通讯作者：
Tuma, Pamela L.
中科院分区：
文献类型：
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作者：
Ramnarayanan, Sai Prasad;Cheng, Christina A.;Tuma, Pamela L.
与直接将新合成的糖磷脂酰肌醇（GPI）锚定和单跨膜结构域（TMD）蛋白从反式高尔基网络传递到顶膜的简单上皮细胞不同，肝细胞使用间接途径：蛋白质被传递到基底外侧结构域，然后选择性地内化并转胞到顶质膜。髓磷脂和淋巴细胞蛋白（MAL）和MAL2分别被确定为直接和间接根尖输送的调节因子。肝细胞缺乏内源性MAL与缺乏直接的根尖靶向一致。MAL表达是否使肝顶端居民进入直接通路？我们发现，MAL在wi - b细胞中的表达诱导胆固醇和富含糖鞘脂的高尔基结构域的形成，这些结构域含有gpi锚定的和单一的TMD顶端蛋白；排除了聚合IgA受体（pIgA-R）、多向根尖和基底外侧的常驻分布。管基底。在表达mal的细胞中，新合成的根尖居民的分娩减少，同时根尖分娩增加；pIgA-R和基底侧住院分娩没有变化。这些数据表明，MAL将选择的肝顶端蛋白重新定向到直接途径中。
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.