The recycling of ERGIC-53 in the early secretory pathway - ERGIC-53 carries a cytosolic endoplasmic reticulum exit determinant interacting with COPII
The recycling of ERGIC-53 in the early secretory pathway - ERGIC-53 carries a cytosolic endoplasmic reticulum exit determinant interacting with COPII
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DOI：
10.1074/jbc.272.50.31801
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发表时间：
1997-12-12
影响因子：
4.8
通讯作者：
Hauri, HP
中科院分区：
文献类型：
--
作者：
Kappeler, F;Klopfenstein, DRC;Hauri, HP
通过定点诱变对细胞内膜凝集素内质网（ER）-高尔基体中间室-53（ERGIC-53）的靶向作用的进一步研究表明，其内腔和跨膜结构域共同赋予ER保留。此外，我们表明，胞质结构域是从ER退出所需的，这表明ERGIC-53携带ER退出决定簇。在C末端的两个苯丙氨酸对于ER-退出是必需的。因此，ERGIC-53包含ER保留以及顺行运输的决定因素，其与二赖氨酸ER回收信号结合，控制ERGIC-53在早期分泌途径中的连续再循环。体外结合研究揭示了ERGIC-53胞质尾肽和COPII外壳组分Sec 23 p之间的特异性苯丙氨酸依赖性相互作用。这些结果表明ERGIC-53的ER-退出是通过其胞质尾部与COPII的Sec23p.Sec24p复合物的直接相互作用介导的，并且在ER水平的蛋白分选通过类似于受体介导的内吞作用或高尔基体到ER逆行转运的机制发生。
Further investigation of the targeting of the intracellular membrane lectin endoplasmic reticulum (ER)-Golgi intermediate compartment-53 (ERGIC-53) by site-directed mutagenesis revealed that its lumenal and transmembrane domains together confer ER retention. In addition we show that the cytoplasmic domain is required for exit from the ER indicating that ERGIC-53 carries an ER-exit determinant. Two phenylalanines at the C terminus are essential for ER-exit. Thus, ERGIC-53 contains determinants for ER retention as well as anterograde transport which, in conjunction with a dilysine ER retrieval signal, control the continuous recycling of ERGIC-53 in the early secretory pathway, In vitro binding studies revealed a specific phenylalanine-dependent interaction between an ERGIC-53 cytosolic tail peptide and the COPII coat component Sec23p. These results suggest that the ER-exit of ERGIC-53 is mediated by direct interaction of its cytosolic tail with the Sec23p.Sec24p complex of COPII and that protein sorting at the level of the ER occurs by a mechanism similar to receptor-mediated endocytosis or Golgi to ER retrograde transport.