VIP17/MAL, a lipid raft-associated protein, is involved in apical transport in MDCK cells
VIP17/MAL, a lipid raft-associated protein, is involved in apical transport in MDCK cells
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DOI：
10.1073/pnas.96.11.6241
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发表时间：
1999-05-25
影响因子：
11.1
通讯作者：
Simons, K
中科院分区：
文献类型：
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作者：
Cheong, KH;Zacchetti, D;Simons, K
顶端蛋白通过一种涉及鞘脂 - 胆固醇筏的机制从反面高尔基体网络分选并运输到质膜。在本文中，我们报道了改变VIP17/MAL水平的影响，VIP17/MAL是一种定位于高尔基体后运输小泡以及MDCK细胞顶端细胞表面的四次跨膜蛋白。VIP17/MAL的过表达通过增加顶端运输并似乎扩大了顶端细胞表面区域，扰乱了MDCK细胞层的形态。另一方面，针对VIP17/MAL的反义RNA表达导致不同顶端蛋白标记物在高尔基体中积累和/或顶端运输受损，这些标记物包括流感病毒血凝素、分泌蛋白簇集素（gp80）、跨膜蛋白gp114以及一种糖基磷脂酰肌醇锚定蛋白。然而，反义RNA表达并不影响E - 钙黏蛋白在基底外侧表面的分布。由于VIP17/MAL与鞘脂 - 胆固醇筏相关联，这些数据提供了功能性证据，表明该蛋白参与顶端运输，并且可能是将脂质筏与顶端货物聚集以形成顶端运输载体的机制的一个组成部分。
Apical proteins are sorted and delivered from the trans-Golgi network to the plasma membrane by a mechanism involving sphingolipid-cholesterol rafts. In this paper, we report the effects of changing the levels of VIP17/MAL, a tetraspan membrane protein localized to post-Golgi transport containers and the apical cell surface in MDCK cells, Overexpression of VIP17/MAL disturbed the morphology of the MDCK cell layers by increasing apical delivery and seemingly expanding the apical cell surface domains. On the other hand, expression of antisense RNA directed against VIP17/MAL caused accumulation in the Golgi and/or im paired apical transport of different apical protein markers, i,e,, influenza virus hemagglutinin, the secretory protein clusterin (gp80), the transmembrane protein gp114, and a glycosylphosphatidylinositol-anchored protein, However, antisense RNA expression did not affect the distribution of E-cadherin to the basolateral surface. Because VIP17/MAL associates with sphingolipid-cholesterol rafts, these data provide functional evidence that this protein is involved in apical transport and might be a component of the machinery clustering lipid rafts with apical cargo to form apical transport carriers.