Regulation of the Sar1 GTPase Cycle Is Necessary for Large Cargo Secretion from the Endoplasmic Reticulum.
Regulation of the Sar1 GTPase Cycle Is Necessary for Large Cargo Secretion from the Endoplasmic Reticulum.
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SAR1 GTPase周期的调节对于内质网的大型货物分泌是必要的。
DOI：
10.3389/fcell.2017.00075
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发表时间：
2017
影响因子：
5.5
通讯作者：
Katada T
中科院分区：
文献类型：
--
作者：
Saito K;Maeda M;Katada T
内质网 (ER) 内合成的蛋白质通过外壳蛋白复合物 II (COPII) 包被的囊泡转运至高尔基体。 COPII 包被囊泡的形成受 Sar1 的 GTPase 循环调节。活化的 Sar1 被招募到 ER 膜上，并与货物和内层复合物形成出芽前复合物。然后外层复合物刺激 Sar1 失活并完成囊泡形成。形成运输载体的机制在物种间是非常保守的；然而，在哺乳动物细胞中，一些货物分子（例如胶原蛋白和乳糜微粒）太大，无法容纳在传统的 COPII 包被囊泡中。因此，从 ER 输出需要特殊的货物受体复合物。 cTAGE5/TANGO1 复合物及其亚型已被确定为这些大分子的货物受体。最近的报告表明，cTAGE5/TANGO1 复合物与 GEF 和 Sar1 的 GAP 相互作用，并严格调节其 GTPase 循环以完成大量货物的分泌。
Proteins synthesized within the endoplasmic reticulum (ER) are transported to the Golgi via coat protein complex II (COPII)-coated vesicles. The formation of COPII-coated vesicles is regulated by the GTPase cycle of Sar1. Activated Sar1 is recruited to ER membranes and forms a pre-budding complex with cargoes and the inner-coat complex. The outer-coat complex then stimulates Sar1 inactivation and completes vesicle formation. The mechanisms of forming transport carriers are well-conserved among species; however, in mammalian cells, several cargo molecules such as collagen, and chylomicrons are too large to be accommodated in conventional COPII-coated vesicles. Thus, special cargo-receptor complexes are required for their export from the ER. cTAGE5/TANGO1 complexes and their isoforms have been identified as cargo receptors for these macromolecules. Recent reports suggest that the cTAGE5/TANGO1 complex interacts with the GEF and the GAP of Sar1 and tightly regulates its GTPase cycle to accomplish large cargo secretion.