Lim Anne, Moussavi Nik Seyyed Hani, Ebrahimie Esmaeil, Lardelli Michael
Alzheimer's disease Genetics Laboratory, School of Molecular and Biomedical Science, The University of Adelaide, Adelaide, South Australia, Australia,
Dev Genes Evol. 2015 Jun;225(3):171-8. doi: 10.1007/s00427-015-0500-9. Epub 2015 May 5.
NICASTRIN is a component of the aspartyl protease γ-secretase complex which is involved in intramembranous cleavage of type I transmembrane proteins, notably the Notch receptor proteins and the AMYLOID BETA A4 PRECURSOR PROTEIN (APP). This study aimed to characterize the orthologue of the human NICASTRIN (NCSTN) gene in zebrafish, an advantageous model organism for the study of human disease. Zebrafish Nicastrin protein was predicted to possess the conserved glutamate 333 residue and DYIGS motif of human NCSTN that are important for substrate recognition/processing in γ-secretase. Quantitative real-time RT-PCR revealed the profile of relative zebrafish nicastrin (ncstn) transcript levels in embryos at different times during development and in adult tissues. The analysis of synteny conservation revealed local rearrangements of ncstn and another gene, mpz, relative to copa, and pex19. In situ hybridization showed higher relative levels of ncstn transcripts in the developing brain and otic vesicles of embryos at 24 and 48 h post fertilization, respectively. Our observations are consistent with a role for Ncstn protein in Notch signaling within the proliferative ventricular zone of the developing central nervous system.
尼卡斯特林是天冬氨酸蛋白酶γ-分泌酶复合物的一个组成部分，该复合物参与I型跨膜蛋白的膜内切割，特别是Notch受体蛋白和淀粉样β蛋白前体蛋白（APP）。本研究旨在鉴定斑马鱼中人类尼卡斯特林（NCSTN）基因的直系同源物，斑马鱼是研究人类疾病的一种优势模式生物。预测斑马鱼尼卡斯特林蛋白具有人类NCSTN保守的谷氨酸333残基和DYIGS基序，这些对于γ-分泌酶中的底物识别/加工很重要。定量实时RT-PCR揭示了斑马鱼尼卡斯特林（ncstn）转录本在胚胎发育不同时期以及成体组织中的相对水平概况。共线性保守分析揭示了相对于copa和pex19，ncstn和另一个基因mpz的局部重排。原位杂交显示，在受精后24小时和48小时的胚胎发育中的脑和耳囊中，ncstn转录本的相对水平较高。我们的观察结果与Ncstn蛋白在发育中的中枢神经系统增殖性脑室区的Notch信号传导中发挥的作用一致。
