Gene Regulation and Expression, School of Life Sciences, University of Dundee, Dundee DD1 5EH, United Kindom.
Gene Regulation and Expression, School of Life Sciences, University of Dundee, Dundee DD1 5EH, United Kindom; Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, 6525GA Nijmegen, The Netherlands.
J Biol Chem. 2020 Jun 26;295(26):8636-8646. doi: 10.1074/jbc.RA119.010312. Epub 2020 Feb 24.
-GlcNAcylation is an abundant post-translational modification in neurons. In mice, an increase in -GlcNAcylation leads to defects in hippocampal synaptic plasticity and learning. -GlcNAcylation is established by two opposing enzymes: -GlcNAc transferase (OGT) and -GlcNAcase (OGA). To investigate the role of OGA in elementary learning, we generated catalytically inactive and precise knockout alleles ( and , respectively) in Adult and flies lacking -GlcNAcase activity showed locomotor phenotypes. Importantly, both lines exhibited deficits in habituation, an evolutionarily conserved form of learning, highlighting that the requirement for -GlcNAcase activity for cognitive function is preserved across species. Loss of -GlcNAcase affected a number of synaptic boutons at the axon terminals of larval neuromuscular junction. Taken together, we report behavioral and neurodevelopmental phenotypes associated with alleles and show that Oga contributes to cognition and synaptic morphology in .
糖基化是神经元中一种丰富的翻译后修饰。在小鼠中，糖基化的增加导致海马突触可塑性和学习缺陷。糖基化是由两种相反的酶建立的：糖基转移酶（OGT）和糖基水解酶（OGA）。为了研究 OGA 在基本学习中的作用，我们在 成年 和 果蝇中生成了催化失活和精确敲除的 等位基因（和 ，分别），这些果蝇缺乏糖基水解酶活性。重要的是，两条 线都表现出习惯化缺陷，这是一种进化上保守的学习形式，这表明糖基水解酶活性对认知功能的需求在物种间是保守的。糖基水解酶的缺失影响了幼虫神经肌肉接头轴突末梢的许多突触末梢。总之，我们报告了与 等位基因相关的行为和神经发育表型，并表明 Oga 有助于 的认知和突触形态。
