LEPROTL1在胶原蛋白从内质网输出过程中的机制研究

真核细胞中的内质网是由连续的管状和片状结构组成的复杂网络，内质网上COPII介导的蛋白输出过程是组织及细胞结构和功能稳定的基础，然而学界对COPII转运大分子货物蛋白的机制尚缺乏深入了解。胶原蛋白作为典型的大分子货物蛋白，它从内质网的输出需要巨型管状COPII小泡的协助。我们通过在线虫中的遗传筛选，发现了一个可以定位于COPII小泡的潜在成管膜蛋白LEPROTL1，同时LEPROTL1的缺失会导致胶原蛋白COL7A1阻遏于内质网中。本课题期望通过研究LEPROTL1对COL7A1转运调控的分子机制，阐明成管蛋白在包被COL7A1的管状囊泡生成和转运中的作用，加深对大分子货物蛋白转运机制的了解，为胶原蛋白异常引起的疾病研究提供新的科学依据。

Morphologically, as one continuous membrane system, the ER consists of cylindrical tubules and cisternal sheets in eukaryotic cells. The COPII-mediated export of proteins from the endoplasmic reticulum (ER) is fundamental to the ongoing maintenance of cell and tissue structure and function. Due to limited approaches and tools in the field, much is unknown with respect to the molecular mechanism of COPII-mediated export of large-sized cargoes, especially, collagens. Collagen is a typical large-sized cargo protein, and its output from the endoplasmic reticulum needs the assistance of giant tubular COPII vesicles. Through genetic screening in C. elegans, we found a potential tubule-forming protein LEPROTL1 that can be located in COPII vesicles. Meanwhile, the deletion of LEPROTL1 will cause collagen COL7A1 to be repressed in the endoplasmic reticulum. This project hopes to explore the molecular mechanism of LEPROTL1 on the regulation of COL7A1 transport, clarify the role of tubule-forming proteins in the formation and transport of COL7A1-export tubule, and deepen the understanding of the transport mechanism of large cargo molecules. Our studies can be profoundly important in the design of strategies to combat multiple diseases caused by abnormal collagen.