Arrestin2 expression selectively increases during neural differentiation
Arrestin2 expression selectively increases during neural differentiation
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DOI：
10.1111/j.1471-4159.2004.02830.x
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发表时间：
2004-12-01
影响因子：
4.7
通讯作者：
Gurevich, VV
中科院分区：
文献类型：
--
作者：
Gurevich, EV;Benovic, JL;Gurevich, VV
抑制蛋白和G蛋白偶联受体激酶（GRKs）是G蛋白偶联受体同源脱敏的关键参与者。两种非视觉抑制蛋白arrestin 2和3以及五种GRK（GRK 2、3、4、5和6）参与许多受体的脱敏。在这里，我们证明了在产前发育过程中arrestin 2表达的稳定增加。与增殖区相比，分化区中arrestin 2 mRNA的密度更高，而arrestin 3 mRNA显示相反的分布。在胚胎第14天，抑制蛋白的浓度是相似的（32-34 nm）。在发育后期，arrestin 2表达升高，导致出生时arrestin 2超过arrestin 3四倍（48对11 ng/mg蛋白或102对25 nm）。在GRKs中，只有GRK 5随着胚胎年龄的增长而增加，从E14时的124 nm增加到出生时的359 nm。类似地，培养的前体细胞、神经球的体外分化导致抑制蛋白2的显著上调，导致> 20倍过量的抑制蛋白2（160对7 nm）。GRK 5是唯一一个随着神经球分化而增加的亚型，尽管这种变化只有大约两倍。这些数据表明与神经发育相关的arrestin 2表达的选择性增加，并表明arrestin 2在神经分化中的特定但未被认识的作用。
Arrestins and G protein-coupled receptor kinases (GRKs) are key players in homologous desensitization of G protein-coupled receptors. Two non-visual arrestins, arrestin2 and 3, and five GRKs (GRK2, 3, 4, 5 and 6) are involved in desensitization of many receptors. Here, we demonstrate a steady increase in arrestin2 expression during prenatal development. The density of arrestin2 mRNA is higher in differentiated areas as compared with proliferative zones, whereas arrestin3 mRNA shows the opposite distribution. At embryonic day 14, concentrations of arrestin proteins are similar (32-34 nm). Later in development, arrestin2 expression rises, leading to a fourfold excess of arrestin2 over arrestin3 at birth (48 vs. 11 ng/mg protein or 102 vs. 25 nm). Among GRKs, only GRK5 increased with embryonic age from 124 nm at E14 to 359 nm at birth. Similarly, in vitro differentiation of cultured precursor cells, neurospheres, leads to a significant up-regulation of arrestin2 resulting in > 20-fold excess of arrestin2 (160 vs. 7 nm). GRK5 is the only subtype increased with neurosphere differentiation, although the change is only about twofold. The data demonstrate selective increases in the expression of arrestin2 associated with neural development and suggest specific yet unappreciated roles for arrestin2 in neural differentiation.