BNIP-2调控E-cadherin细胞内分选运输的机制研究

细胞膜表面蛋白内吞到早期内吞体后可直接回到膜上、再循环体或TGN进行再循环利用，或转运至溶酶体降解。内吞蛋白的分选路径已被大量研究，但关于细胞是如何决定蛋白分选仍知之甚少。课题组初步研究发现一个拥有BCH域的蛋白BNIP-2可通过调控膜蛋白E-cadherin影响斑马鱼胚胎原肠胚形成。BNIP-2除已知的改变细胞形态、抑制乳腺癌细胞迁移和在成肌细胞分化中的作用外，在其他组织或细胞中的功能仍存在着许多未知。我们进一步研究发现BNIP-2可抑制E-cadherin的降解，表明BNIP-2在调控E-cadherin内吞和细胞内分选中起到关键作用。本课题将继续利用生物化学、分子生物学和细胞生物学等手段，阐明BNIP-2调控E-cadherin以及其他膜蛋白运输分选的分子机制。本项目的开展不仅可揭示BNIP-2在细胞运输领域的全新功能，也为深入了解细胞是如何决定膜表面蛋白内吞后的分选机制提供新思路。

Endocytosed proteins can be sorted to trans-Golgi network, recycling endosome or the plasma membrane for recycling, or be sorted to lysosomes for degradation. The molecular mechanisms that determine the recycling versus degradation pathways for cargo proteins are poorly understood. Here, we found that knockdown of BNIP-2, a protein containing a highly conserved BNIP-2 and Cdc42GAP homology (BCH) domain, leads to the deregulation of membrane protein E-cadherin and affects gastrulation in zebrafish. Besides controlling the cell protrusion, retarding breast cancer cell migration and participating in myoblast differentiation, the role of BNIP-2 in other tissue and cellular processes remains unknown. Our study further shows that knockdown of BNIP-2 enhances the sorting of endocytosed E-cadherin into lysosomes and accelerates E-cadherin degradation, suggesting a key role of BNIP-2 in regulating the endocytosis and sorting of E-cadherin. Herein, we propose to examine and elucidate the molecular mechanism of BNIP-2 regulating the intracellular trafficking of E-cadherin by biochemistry, molecular biology and cell biology methods. We then expect to reveal a new function of BNIP-2 in the filed of membrane intracellular trafficking and provide a better understanding of how cells determine the fate of protein after endocytosis.