IGF-2r的结构和功能及其在胚胎发育中的作用

IGF-2r structure, function and its role in the embryonic development

胰岛素样生长因子-2受体(insulin-like growth factor-2 receptor,IGF-2r)和非阳离子依赖型甘露糖-6-磷酸受体(cation-independent mannose-6-phosphate receptor,CI-MPR)为同一分子,属多结构域跨膜糖蛋白。IGF-2r与阳离子依赖型M6P受体(cation-dependent mannose-6-phosphotase receptor,CD-MPR) 共同介导溶酶体酶的分选和转运过程,对溶酶体的形成起重要作用。IGF-2/M6P受体除能与溶酶体酶、TGF-β前体等M6P配体结合外,还能与非糖基化的IGF-2、视黄酸等作用,调节蛋白质的转运和跨膜信号传导等活动。IGF-2r为父源性印迹(paternal imprinted)基因,基因的印迹、表达受基因印迹控制区(imprinting control region,ICR)的甲基化差异修饰所调控。IGF-2r基因表达缺失出现胎儿肥大、心脏和胎盘发育不全、围产期死亡等异常现象,证明IGF-2r在胚胎发育过程中起重要作用。

The insulin-like growth factor-II receptor is a multifunctional single transmembrane glycoprotein with multi-domain, which is identical to the cation-independent mannose-6-phosphate （M6P） receptor. The IGF-Ⅱ/ M6P receptor, along with the cation-dependent M6P （CD-M6P） receptor, mediates the intercellular sorting and trafficking of M6P-containing lysosomal enzymes from the trans-Golgi network （TGN） to lysosomes. In addition to lysosomal enzymes, the IGF-Ⅱ/M6P receptor also binds a diverse spectrum of other M6P containing proteins, including transforming growth factor-β （TGF-β） precursor, as well as non-M6P-containing retinoic acid and IGF-2, thereby regulates a myriad of biological processes, such as protein trafficking and transmembrane signal transduction, to affect the developmental growth and metablism. IGF-2r gene is generally imprinted on the paternally inherited allele and expressed from maternal allele depending on the imprinting control region （ICR） differentially methylated. The IGF-Ⅱ/M6P receptor plays a critical role in the embryonic development and is supported by the phenotypes that the disruption of the gene resulted in disproportional overgrowth, particularly of the heart and placenta during post-implantation, and perinatal lethality.