title: Developmental regulation of protein O-GlcNAcylation, O-GlcNAc transferase, and O-GlcNAcase in mammalian brain.
abstract: O-GlcNAcylation is a common posttranslational modification of nucleocytoplasmic proteins by β-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 β-N-acetylglucosaminidase (O-GlcNAcase, OGA), respectively. 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 in neuronal cell bodies and processes, further suggesting the role of O-GlcNAc modification of neuronal proteins in the brain. These studies provide fundamental knowledge of age-dependent protein modification by O-GlcNAc and will help guide future studies on the role of O-GlcNAcylation in the mammalian brain.
authors.affiliation: Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, New York, United States of America.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Li
authors.forename: Yang
authors.initials: Y
authors.lastname: Yu
authors.forename: Jianhua
authors.initials: J
authors.lastname: Shi
authors.forename: Zhihou
authors.initials: Z
authors.lastname: Liang
authors.forename: Xiaoqin
authors.initials: X
authors.lastname: Run
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.forename: Chun-ling
authors.initials: CL
authors.lastname: Dai
authors.forename: Inge
authors.initials: I
authors.lastname: Grundke-Iqbal
authors.forename: Khalid
authors.initials: K
authors.lastname: Iqbal
authors.forename: Fei
authors.initials: F
authors.lastname: Liu
authors.forename: Cheng-Xin
authors.initials: CX
authors.lastname: Gong
mesh_terms: D000117:Acetylglucosamine / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000196:embryology / Q000201:enzymology / Q000254:growth & development / Q000378:metabolism*; D005260:Female; D007527:Isoenzymes / Q000378:metabolism; D017351:N-Acetylglucosaminyltransferases / Q000378:metabolism*; D010766:Phosphorylation; D011247:Pregnancy; D011499:Protein Processing, Post-Translational; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D001619:beta-N-Acetylhexosaminidases / Q000378:metabolism*
chemical_list: D007527:Isoenzymes; D017351:N-Acetylglucosaminyltransferases; C063057:UDP-N-acetylglucosamine-peptide beta-N-acetylglucosaminyltransferase; C110628:hexosaminidase C; D001619:beta-N-Acetylhexosaminidases; D000117:Acetylglucosamine