ARH cooperates with AP-1B in the exocytosis of LDLR in polarized epithelial cells
ARH cooperates with AP-1B in the exocytosis of LDLR in polarized epithelial cells
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DOI：
10.1083/jcb.201012121
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发表时间：
2011-04-04
影响因子：
7.8
通讯作者：
Foelsch, Heike
中科院分区：
文献类型：
--
作者：
Kang, Richard S.;Foelsch, Heike
常染色体隐性高胆固醇血症蛋白（ARH）因其在网格蛋白介导的低密度脂蛋白受体（LDLR）内吞作用中的作用而闻名。在摄取过程中，ARH直接结合LDLR胞质尾区的FxNPxY信号。有趣的是，相同的FxNPxY基序用于LDLR从再循环内体（RE）的基底外侧胞吐，这是由上皮特异性网格蛋白衔接子AP-1B促进的。然而，AP-1B既不直接与FxNPxY基序相互作用，也不与LDLR的第二个更远侧的Yxx空集合分选基序相互作用。在这里，我们表明，ARH共定位和合作与AP-1B在REs. Knockdown的ARH极化上皮细胞导致特定的顶端错配截短的LDLR，它只编码FxNPxY基序（LDLR-CT 27）。此外，ARH中的突变旨在破坏ARH与AP-1B的相互作用，特异性消除LDLR-CT 27的胞吐作用。我们的结论是，除了其作用的内吞作用，ARH合作与AP-1B在基底外侧胞吐低密度脂蛋白受体从RE。
The autosomal recessive hypercholesterolemia protein (ARH) is well known for its role in clathrin-mediated endocytosis of low-density lipoprotein receptors (LDLRs). During uptake, ARH directly binds to the FxNPxY signal in the cytoplasmic tail of LDLR. Interestingly, the same FxNPxY motif is used in basolateral exocytosis of LDLR from recycling endosomes (REs), which is facilitated by the epithelial-specific clathrin adaptor AP-1B. However, AP-1B directly interacts with neither the FxNPxY motif nor the second more distally located Yxxempty set sorting motif of LDLR. Here, we show that ARH colocalizes and cooperates with AP-1B in REs. Knockdown of ARH in polarized epithelial cells leads to specific apical missorting of truncated LDLR, which encodes only the FxNPxY motif (LDLR-CT27). Moreover, a mutation in ARH designed to disrupt the interaction of ARH with AP-1B specifically abrogates exocytosis of LDLR-CT27. We conclude that in addition to its role in endocytosis, ARH cooperates with AP-1B in basolateral exocytosis of LDLR from REs.