Intracellular mechanisms of molecular recognition and sorting for transport of large extracellular matrix molecules
Intracellular mechanisms of molecular recognition and sorting for transport of large extracellular matrix molecules
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DOI：
10.1073/pnas.1609571113
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发表时间：
2016-10-11
影响因子：
11.1
通讯作者：
Bachinger, Hans Peter
中科院分区：
文献类型：
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作者：
Ishikawa, Yoshihiro;Ito, Shinya;Bachinger, Hans Peter
细胞外基质（ECM）蛋白在粗内质网（rER）中生物合成，并通过高尔基体运输到细胞外空间。外壳蛋白复合物II （COPII）运输囊泡直径约为60- 90nm。然而，一些ECM分子要大得多，可达几百纳米。因此，需要特殊的COPII囊泡来包裹和运输这些分子。跨膜蛋白转运和高尔基组织1 （TANGO1）促进胶原装载到特殊的囊泡中。TANGO1的Src homology 3 （SH3）结构域被提出用于识别胶原分子，但SH3结构域如何识别各种类型的胶原尚不清楚。此外，大的非胶原ECM分子是如何从内质网转运到高尔基体的？在这里，我们发现热休克蛋白（Hsp） 47作为一种引导分子，通过与TANGO1的SH3结构域相互作用，将胶原引导到特殊的囊泡。我们还考虑胶原分泌模型是否适用于其他大ECM分子。
Extracellular matrix (ECM) proteins are biosynthesized in the rough endoplasmic reticulum (rER) and transported via the Golgi apparatus to the extracellular space. The coat protein complex II (COPII) transport vesicles are approximately 60-90 nm in diameter. However, several ECM molecules are much larger, up to several hundreds of nanometers. Therefore, special COPII vesicles are required to coat and transport these molecules. Transmembrane Protein Transport and Golgi Organization 1 (TANGO1) facilitates loading of collagens into special vesicles. The Src homology 3 (SH3) domain of TANGO1 was proposed to recognize collagen molecules, but how the SH3 domain recognizes various types of collagen is not understood. Moreover, how are large noncollagenous ECM molecules transported from the rER to the Golgi? Here we identify heat shock protein (Hsp) 47 as a guide molecule directing collagens to special vesicles by interacting with the SH3 domain of TANGO1. We also consider whether the collagen secretory model applies to other large ECM molecules.