当前位置: X-MOL 学术Crit. Rev. Biochem. Mol. Biol. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Retinol-binding protein 2 (RBP2): biology and pathobiology.
Critical Reviews in Biochemistry and Molecular Biology ( IF 6.5 ) Pub Date : 2020-05-28 , DOI: 10.1080/10409238.2020.1768207
William S Blaner 1 , Pierre-Jacques Brun 1 , Rossana M Calderon 1 , Marcin Golczak 2
Affiliation  

Retinol-binding protein 2 (RBP2; originally cellular retinol-binding protein, type II (CRBPII)) is a 16 kDa cytosolic protein that in the adult is localized predominantly to absorptive cells of the proximal small intestine. It is well established that RBP2 plays a central role in facilitating uptake of dietary retinoid, retinoid metabolism in enterocytes, and retinoid actions locally within the intestine. Studies of mice lacking Rbp2 establish that Rbp2 is not required in times of dietary retinoid-sufficiency. However, in times of dietary retinoid-insufficiency, the complete lack of Rbp2 gives rise to perinatal lethality owing to RBP2 absence in both placental (maternal) and neonatal tissues. Moreover, when maintained on a high-fat diet, Rbp2-knockout mice develop obesity, glucose intolerance and a fatty liver. Unexpectedly, recent investigations have demonstrated that RBP2 binds long-chain 2-monoacylglycerols (2-MAGs), including the canonical endocannabinoid 2-arachidonoylglycerol, with very high affinity, equivalent to that of retinol binding. Crystallographic studies establish that 2-MAGs bind to a site within RBP2 that fully overlaps with the retinol binding site. When challenged orally with fat, mucosal levels of 2-MAGs in Rbp2 null mice are significantly greater than those of matched controls establishing that RBP2 is a physiologically relevant MAG-binding protein. The rise in MAG levels is accompanied by elevations in circulating levels of the hormone glucose-dependent insulinotropic polypeptide (GIP). It is not understood how retinoid and/or MAG binding to RBP2 affects the functions of this protein, nor is it presently understood how these contribute to the metabolic and hormonal phenotypes observed for Rbp2-deficient mice.



中文翻译:

视黄醇结合蛋白 2 (RBP2):生物学和病理生物学。

视黄醇结合蛋白 2(RBP2;最初是细胞视黄醇结合蛋白,II 型(CRBPII))是一种 16 kDa 的胞质蛋白,在成人中主要定位于近端小肠的吸收细胞。众所周知,RBP2 在促进膳食类视黄醇的摄取、肠细胞中的类视黄醇代谢和肠道内局部类视黄醇的作用方面发挥着核心作用。对缺乏Rbp2的小鼠的研究表明,在膳食类维生素 A 充足的时期不需要Rbp2。然而,在膳食类视黄醇不足的情况下,由于胎盘(母体)和新生儿组织中均缺乏RBP2,因此完全缺乏Rbp2会导致围产期致死率。此外,当维持高脂肪饮食时,Rbp2- 基因敲除小鼠会出现肥胖、葡萄糖耐受不良和脂肪肝。出乎意料的是,最近的研究表明,RBP2 结合长链 2-单酰基甘油 (2-MAG),包括经典的内源性大麻素 2-花生四烯酸甘油,具有非常高的亲和力,相当于视黄醇的结合。晶体学研究确定 2-MAG 与 RBP2 内的一个位点结合,该位点与视黄醇结合位点完全重叠。当用脂肪口服刺激时Rbp2中 2-MAG 的粘膜水平空小鼠显着大于匹配对照的小鼠,确定 RBP2 是生理相关的 MAG 结合蛋白。MAG 水平的升高伴随着激素葡萄糖依赖性促胰岛素多肽 (GIP) 的循环水平升高。尚不清楚类视黄醇和/或 MAG 与 RBP2 的结合如何影响该蛋白质的功能,目前也不了解这些对观察到的Rbp2 缺陷小鼠的代谢和激素表型有何贡献。

更新日期:2020-05-28
down
wechat
bug