developmental regulation of protein o-glcnacylation, o-glcnac transferase, and o-glcnacase in mammalian brain发育调控的蛋白质o-glcnacylation、o-glcnac转移酶和o-glcnacase在哺乳动物大脑.pdfVIP

Developmental Regulation of Protein O-GlcNAcylation, O-GlcNAc Transferase, and O-GlcNAcase in Mammalian Brain Ying Liu1.¤a, Xiaojing Li1., Yang Yu1¤b, Jianhua Shi1,2, Zhihou Liang1¤c, Xiaoqin Run1¤c, Yi Li1¤d, Chun- 1 1 1 1,2 1 ling Dai , Inge Grundke-Iqbal , Khalid Iqbal , Fei Liu , Cheng-Xin Gong * 1 Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York, United States of America, 2 Jiangsu Key Laboratory of Neuroregeneration, Nantong University, Nantong, Jiangsu, China Abstract O-GlcNAcylation is a common posttranslational modification of nucleocytoplasmic proteins by b-N-acetylglucosamine (GlcNAc). The dynamic addition and removal of O-GlcNAc groups to and from proteins are catalyzed by O-linked N- acetylglucosamine transferase (O-GlcNAc transferase, OGT) and b-N-acetylglucosaminidase (O-GlcNAcase, OGA), respec- tively. O-GlcNAcylation often modulates protein phosphorylation and regulates several cellular signaling and functions, especially in the brain. However, its developmental regulation is not well known. Here, we studied protein O-GlcNAcylation, OGT, and OGA in the rat brain at various ages from embryonic day 15 to the age of 2 years. We found a gradual decline of global protein O-GlcNAcylation during developmental stages and adulthood. This decline correlated positively to the total protein phosphorylation at serine residues, but not at threonine residues. The expression of OGT and OGA isoforms was regulated differently at various ages. Immunohistochemical studies revealed ubiquitous distribution of O-GlcNAcylation at all ages. Strong immunostaining of O-GlcNAc, OGT, and OGA was observed mostly