Retinol-binding protein 2 (RBP2): biology and pathobiology.
Retinol-binding protein 2 (RBP2): biology and pathobiology.
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DOI：
10.1080/10409238.2020.1768207
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发表时间：
2020-04
影响因子：
6.5
通讯作者：
Golczak M
中科院分区：
文献类型：
--
作者：
Blaner WS;Brun PJ;Calderon RM;Golczak M
视黄醇结合蛋白2（RBP 2;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。已经确定，RBP 2在促进膳食类维生素A的摄取、肠细胞中的类维生素A代谢和肠内局部的类维生素A作用中起核心作用。对缺乏Rbp 2的小鼠的研究证实，在饮食类维生素A充足的情况下不需要Rbp 2。然而，在膳食类维生素A不足的时候，由于胎盘（母体）和新生儿组织中RBP 2的缺乏，RBP 2的完全缺乏引起围产期死亡。此外，当维持高脂肪饮食时，Rbp 2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，RBP 2结合长链2-单酰基甘油（2-MAG），包括典型的内源性大麻素2-花生四烯酸甘油，具有非常高的亲和力，相当于视黄醇结合。晶体学研究确定2-MAG结合至RBP 2内与视黄醇结合位点完全重叠的位点。当用脂肪经口攻击时，Rbp 2缺失小鼠中2-MAG的粘膜水平显著大于匹配对照小鼠的粘膜水平，从而确立RBP 2是生理学相关的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）的循环水平的升高。目前还不清楚类维生素A和/或MAG与RBP 2的结合如何影响这种蛋白质的功能，也不清楚这些如何有助于在Rbp 2缺陷小鼠中观察到的代谢和激素表型。
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.
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影响因子：
3.7
作者：
Chon SH;Douglass JD;Zhou YX;Malik N;Dixon JL;Brinker A;Quadro L;Storch J
通讯作者：
Storch J
影响因子：
3.5
作者：
Bhat, PV
通讯作者：
Bhat, PV
影响因子：
6.5
作者：
Douglass, John D.;Zhou, Yin Xiu;Storch, Judith
通讯作者：
Storch, Judith
DOI：
10.1073/pnas.82.14.4707
发表时间：
1985-01-01
影响因子：
11.1
作者：
CROW, JA;ONG, DE
通讯作者：
ONG, DE
DOI：
10.1016/j.plefa.2018.11.016
发表时间：
2019-01-01
影响因子：
3
作者：
Chanda, Dipanjan;Neumann, Dietbert;Glatz, Jan F. C.
通讯作者：
Glatz, Jan F. C.