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首页> 外文期刊>Molecular and Cellular Biology >A Novel GGA-Binding Site Is Required for Intracellular Sorting Mediated by Stabilin-1
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A Novel GGA-Binding Site Is Required for Intracellular Sorting Mediated by Stabilin-1

机译：Stabilin-1介导的细胞内分选需要一个新型的GGA结合位点。

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Stabilin-1 is a unique scavenger receptor that combines endocytic and intracellular sorting functions in macrophages. Stabilin-1 mediates the endocytosis of acetylated low-density lipoprotein (acLDL), SPARC, and growth hormone family member placental lactogen (PL). At the same time, stabilin-1 is involved in trans-Golgi network-to-endosome routing of the endogenous chitinase-like protein SI-CLP (stabilin-interacting chitinase-like protein). A DDSLL motif in the cytoplasmic tail of stabilin-1 interacts with GGA adaptors; however, the deletion of DDSLL reduces but does not abrogate this interaction. Here, we identified a novel GGA-binding site, EDDADDD, in the cytoplasmic tail of stabilin-1. The deletion of EDDADDD impaired and the deletion of both the DDSLL and EDDADDD sites abrogated the interaction of stabilin-1 with GGAs. The surface exposure of stabilin-1 and stabilin-1-mediated endocytosis of acLDL, SPARC, and PL were not affected by the deletion either of DDSLL or EDDADDD or both. At the same time, both GGA-binding sites were necessary for the intracellular sorting of SI-CLP performed by stabilin-1. Our data indicate that the novel GGA-binding site EDDADDD is essential for stabilin-1-mediated intracellular sorting but is not required for endocytosis.
机译：Stabilin-1是一种独特的清除剂受体，在巨噬细胞中结合了内吞和细胞内分选功能。 Stabilin-1介导乙酰化低密度脂蛋白（acLDL），SPARC和生长激素家族成员胎盘乳原（PL）的内吞作用。同时，stabiin-1参与了内源几丁质酶样蛋白SI-CLP（ s tabilin- i interacting）的反高尔基网络到内体的路由 c hitinase- l ike p rotein）。在stabilin-1胞质尾巴中的DDSLL基序与GGA衔接子相互作用。但是，删除DDSLL会减少但不会取消此交互。在这里，我们在stabilin-1的细胞质尾部鉴定了一个新的GGA结合位点EDDADDD。 EDDADDD的删除受损，而DDSLL和EDDADDD位点的删除则废除了Staabilin-1与GGA的相互作用。 acLDL，SPARC和PL的stabilin-1和stabilin-1介导的内吞作用的表面暴露不受DDSLL或EDDADDD或两者缺失的影响。同时，两个GGA结合位点对于stabilin-1进行的SI-CLP细胞内分选都是必需的。我们的数据表明，新颖的GGA结合位点EDDADDD对于stabilin-1介导的细胞内分选是必不可少的，但对于胞吞作用并不是必需的。

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