College of Optometry, The Ohio State University, 338 West 10th Avenue, Columbus, OH 43210, USA.
Neuroscience. 2010 Sep 1;169(3):1376-91. doi: 10.1016/j.neuroscience.2010.05.081. Epub 2010 Jun 9.
Guanine nucleotide-binding protein beta3 (GNB3) is an isoform of the beta subunit of the heterotrimeric G protein second messenger complex that is commonly associated with transmembrane receptors. The presence of GNB3 in photoreceptors, and possibly bipolar cells, has been confirmed in murine, bovine and primate retinas [Lee RH, Lieberman BS, Yamane HK, Bok D, Fung BK (1992) J Biol Chem 267:24776-24781; Peng YW, Robishaw JD, Levine MA, Yau KW (1992) Proc Natl Acad Sci U S A 89:10882-10886; Huang L, Max M, Margolskee RF, Su H, Masland RH, Euler T (2003) J Comp Neurol 455:1-10]. Studies have indicated that a mutation in the GNB3 gene causes progressive retinopathy and globe enlargement (RGE) in chickens. The goals of this study were to (1) examine the expression pattern of GNB3 in wild-type and RGE mutant chickens, (2) characterize the types of bipolar cells that express GNB3 and (3) examine whether the expression of GNB3 in the retina is conserved across vertebrate species. We find that chickens homozygous for the RGE allele completely lack GNB3 protein. We find that the pattern of expression of GNB3 in the retina is highly conserved across vertebrate species, including teleost fish (Carassius auratus), frogs (Xenopus laevis), chickens (Gallus domesticus), mice (Mus musculata), guinea-pigs (Cavia porcellus), dogs (Canis familiaris) and non-human primates (Macaca fasicularis). Regardless of the species, we find that GNB3 is expressed by Islet1-positive cone ON-bipolar cells and by cone photoreceptors. In some vertebrates, GNB3-immunoreactivity was observed in both rod and cone photoreceptors. A protein-protein alignment of GNB3 across different vertebrates, from fish to humans, indicates a high degree (>92%) of sequence conservation. Given that analogous types of retinal neurons express GNB3 in different species, we propose that the functions and the mechanisms that regulate the expression of GNB3 are highly conserved.
鸟嘌呤核苷酸结合蛋白β3(GNB3)是异三聚体 G 蛋白第二信使复合物β亚基的一种同工型,通常与跨膜受体相关。在鼠、牛和灵长类动物视网膜中已经证实了 GNB3 存在于光感受器中,并且可能存在于双极细胞中[Lee RH、Lieberman BS、Yamane HK、Bok D、Fung BK(1992)J Biol Chem 267:24776-24781;Peng YW、Robishaw JD、Levine MA、Yau KW(1992)Proc Natl Acad Sci U S A 89:10882-10886;Huang L、Max M、Margolskee RF、Su H、Masland RH、Euler T(2003)J Comp Neurol 455:1-10]。研究表明,GNB3 基因突变会导致鸡的进行性视网膜病变和眼球增大(RGE)。本研究的目的是:(1)研究野生型和 RGE 突变型鸡中 GNB3 的表达模式;(2)描述表达 GNB3 的双极细胞类型;(3)研究 GNB3 在视网膜中的表达是否在脊椎动物中具有保守性。我们发现,RGE 等位基因纯合的鸡完全缺乏 GNB3 蛋白。我们发现,GNB3 在视网膜中的表达模式在包括硬骨鱼(Carassius auratus)、青蛙(Xenopus laevis)、鸡(Gallus domesticus)、小鼠(Mus musculata)、豚鼠(Cavia porcellus)、狗(Canis familiaris)和非人类灵长类动物(Macaca fasicularis)在内的脊椎动物中具有高度的保守性。无论物种如何,我们发现 GNB3 由 Islet1 阳性视锥 ON-双极细胞和视锥细胞表达。在一些脊椎动物中,GNB3-免疫反应性观察到在视杆和视锥细胞中。通过对不同脊椎动物(从鱼类到人类)的 GNB3 进行蛋白-蛋白比对,表明序列高度保守(>92%)。鉴于类似类型的视网膜神经元在不同物种中表达 GNB3,我们推测 GNB3 的功能和调节其表达的机制具有高度保守性。