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Low Rho activity in hepatocytes prevents apical from basolateral cargo separation during trans-Golgi network to surface transport.
Traffic ( IF 3.6 ) Pub Date : 2020-03-12 , DOI: 10.1111/tra.12725 Francisco Lázaro-Diéguez 1 , Anne Müsch 1
Traffic ( IF 3.6 ) Pub Date : 2020-03-12 , DOI: 10.1111/tra.12725 Francisco Lázaro-Diéguez 1 , Anne Müsch 1
Affiliation
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Hepatocytes, the main epithelial cells of the liver, organize their polarized membrane domains differently from ductal epithelia. They also differ in their biosynthetic delivery of single-membrane-spanning and glycophosphatidylinositol-anchored proteins to the apical domain. While ductal epithelia target apical proteins to varying degrees from the trans-Golgi network (TGN) to the apical surface directly, hepatocytes target them first to the basolateral domain, from where they undergo basolateral-to-apical transcytosis. How TGN-to-surface transport differs in both scenarios is unknown. Here, we report that the basolateral detour of a hepatocyte apical protein is due, in part, to low RhoA activity at the TGN, which prevents its segregation from basolateral transport carriers. Activating Rho in hepatocytic cells, which switches their polarity from hepatocytic to ductal, also led to apical-basolateral cargo segregation at the TGN as is typical for ductal cells, affirming a central role for Rho-signaling in different aspects of the hepatocytic polarity phenotype. Nevertheless, Rho-induced cargo segregation was not sufficient to target the apical protein directly; thus, failure to recruit apical targeting machinery also contributes to its indirect itinerary.
中文翻译：
肝细胞中的低 Rho 活性可防止在跨高尔基体网络到表面运输过程中顶端与基底外侧货物分离。
肝细胞是肝脏的主要上皮细胞，其极化膜域的组织方式与导管上皮不同。它们的不同之处还在于将单膜跨膜蛋白和糖磷脂酰肌醇锚定蛋白生物合成递送至顶端结构域。虽然导管上皮不同程度地从跨高尔基体网络（TGN）直接靶向顶端蛋白，但肝细胞首先将它们靶向基底外侧域，从那里它们经历基底外侧到顶端的转胞吞作用。 TGN 到地面的运输在这两种情况下有何不同尚不清楚。在这里，我们报告肝细胞顶端蛋白的基底外侧绕行部分是由于 TGN 处的低 RhoA 活性，这阻止了其与基底外侧运输载体的分离。激活肝细胞中的 Rho，将其极性从肝细胞极性转变为导管极性，也导致 TGN 处的顶端-基底外侧货物分离，这是导管细胞的典型现象，证实了 Rho 信号传导在肝细胞极性表型的不同方面的核心作用。然而，Rho 诱导的货物分离不足以直接靶向顶端蛋白；因此，未能招募顶端靶向机制也导致其间接行程。
更新日期：2020-04-22
中文翻译：
肝细胞中的低 Rho 活性可防止在跨高尔基体网络到表面运输过程中顶端与基底外侧货物分离。
肝细胞是肝脏的主要上皮细胞，其极化膜域的组织方式与导管上皮不同。它们的不同之处还在于将单膜跨膜蛋白和糖磷脂酰肌醇锚定蛋白生物合成递送至顶端结构域。虽然导管上皮不同程度地从跨高尔基体网络（TGN）直接靶向顶端蛋白，但肝细胞首先将它们靶向基底外侧域，从那里它们经历基底外侧到顶端的转胞吞作用。 TGN 到地面的运输在这两种情况下有何不同尚不清楚。在这里，我们报告肝细胞顶端蛋白的基底外侧绕行部分是由于 TGN 处的低 RhoA 活性，这阻止了其与基底外侧运输载体的分离。激活肝细胞中的 Rho，将其极性从肝细胞极性转变为导管极性，也导致 TGN 处的顶端-基底外侧货物分离，这是导管细胞的典型现象，证实了 Rho 信号传导在肝细胞极性表型的不同方面的核心作用。然而，Rho 诱导的货物分离不足以直接靶向顶端蛋白；因此，未能招募顶端靶向机制也导致其间接行程。
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