Department of Brain Development and Neural Regeneration, Tokyo Metropolitan Institute of Medical Science, Setagaya, Tokyo 156-0057, Japan.
Department of Biosciences and Informatics, Faculty of Science and Technology, Keio University, Kohoku, Yokohama, 223-8522, Japan.
Proc Natl Acad Sci U S A. 2017 Apr 11;114(15):3939-3944. doi: 10.1073/pnas.1612943114. Epub 2017 Mar 27.
AMPA-type glutamate receptors (GluAs) mediate fast excitatory transmission in the vertebrate central nervous system (CNS), and their function has been extensively studied in the mature mammalian brain. However, GluA expression begins very early in developing embryos, suggesting that they may also have unidentified developmental roles. Here, we identify developmental roles for GluAs in the ascidian Mammals express Ca-permeable GluAs (Ca-P GluAs) and Ca-impermeable GluAs (Ca-I GluAs) by combining subunits derived from four genes. In contrast, ascidians have a single gene. Taking advantage of the simple genomic GluA organization in ascidians, we knocked down (KD) GluAs in and observed severe impairments in formation of the ocellus, a photoreceptive organ used during the swimming stage, and in resorption of the tail and body axis rotation during metamorphosis to the adult stage. These defects could be rescued by injection of KD-resistant GluAs. GluA KD phenotypes could also be reproduced by expressing a GluA mutant that dominantly inhibits glutamate-evoked currents. These results suggest that, in addition to their role in synaptic communication in mature animals, GluAs also have critical developmental functions.
AMPA 型谷氨酸受体 (GluAs) 在脊椎动物中枢神经系统 (CNS) 中介导快速兴奋性传递,其功能在成熟哺乳动物大脑中得到了广泛研究。然而,GluA 的表达在发育中的胚胎中很早就开始了,这表明它们可能也具有未被识别的发育作用。在这里,我们确定了 GluAs 在 中的发育作用。哺乳动物通过结合来自四个基因的亚基表达钙通透型 GluAs (Ca-P GluAs) 和钙非通透型 GluAs (Ca-I GluAs)。相比之下, 只有一个 基因。利用 中 GluA 简单的基因组组织,我们敲低了 中的 GluAs,并观察到小眼的形成严重受损,小眼是游泳阶段使用的光感受器器官,以及在变态为成体阶段时尾巴和体轴旋转的吸收过程受损。通过注射 KD 抗性 GluAs 可以挽救这些缺陷。通过表达一种显性抑制谷氨酸诱发电流的 GluA 突变体,也可以再现 GluA KD 表型。这些结果表明,除了在成熟动物的突触通讯中发挥作用外,GluAs 还具有关键的发育功能。