Yoo Kyeong-Won, Thiruvarangan Maivannan, Jeong Yun-Mi, Lee Mi-Sun, Maddirevula Sateesh, Rhee Myungchull, Bae Young-Ki, Kim Hyung-Goo, Kim Cheol-Hee
Department of Biology, Chungnam National University, Daejeon 34134, Korea.
Comparative Biomedicine Research Branch, Research Institute, National Cancer Center, Goyang 10408, Korea.
Mol Cells. 2017 Apr;40(4):271-279. doi: 10.14348/molcells.2017.2308. Epub 2017 Mar 28.
Ran-binding protein family member, RanBP9 has been reported in various basic cellular mechanisms and neuropathological conditions including schizophrenia. Previous studies have reported that RanBP9 is highly expressed in the mammalian brain and retina; however, the role of RanBP9 in retinal development is largely unknown. Here, we present the novel and regulatory roles of RanBP9 in retinal development of a vertebrate animal model, zebrafish. Zebrafish embryos exhibited abundant expression of in developing brain tissues as well as in the developing retina. Yeast two-hybrid screening demonstrated the interaction of RanBP9 with Mind bomb, a component of Notch signaling involved in both neurogenesis and neural disease autism. The interaction is further substantiated by co-localization studies in cultured cells. Knockdown of resulted in retinal dysplasia with defective proliferation of retinal cells, downregulation of neuronal differentiation marker , elevation of neural proliferation marker , and alteration of cell cycle marker . Expression of the Müller glial cell marker glutamine synthase was also affected in knockdown morphants. Our results suggest that Mind bomb-binding partner RanBP9 plays a role during retinal cell development of zebrafish embryogenesis.
Ran结合蛋白家族成员RanBP9已在包括精神分裂症在内的各种基本细胞机制和神经病理状况中被报道。先前的研究报道RanBP9在哺乳动物大脑和视网膜中高度表达；然而，RanBP9在视网膜发育中的作用在很大程度上尚不清楚。在这里，我们展示了RanBP9在脊椎动物模型斑马鱼视网膜发育中的新作用和调节作用。斑马鱼胚胎在发育中的脑组织以及发育中的视网膜中均表现出丰富的表达。酵母双杂交筛选表明RanBP9与Mind bomb相互作用，Mind bomb是Notch信号通路的一个组成部分，参与神经发生和神经疾病自闭症。在培养细胞中的共定位研究进一步证实了这种相互作用。敲低RanBP9导致视网膜发育异常，伴有视网膜细胞增殖缺陷、神经元分化标志物下调、神经增殖标志物上调以及细胞周期标志物改变。Müller神经胶质细胞标志物谷氨酰胺合成酶的表达在敲低的形态学突变体中也受到影响。我们的结果表明，与Mind bomb结合的伴侣RanBP9在斑马鱼胚胎发育的视网膜细胞发育过程中发挥作用。
