title: Selective loss of glycogen synthase kinase-3α in birds reveals distinct roles for GSK-3 isozymes in tau phosphorylation.
abstract: Mammalian glycogen synthase kinase-3 (GSK-3), a critical regulator in neuronal signaling, cognition, and behavior, exists as two isozymes GSK-3α and GSK-3β. Their distinct biological functions remains largely unknown. Here, we examined the evolutionary significance of each of these isozymes. Surprisingly, we found that unlike other vertebrates that harbor both GSK-3 genes, the GSK-3α gene is missing in birds. GSK-3-mediated tau phosphorylation was significantly lower in adult bird brains than in mouse brains, a phenomenon that was reproduced in GSK-3α knockout mouse brains. Tau phosphorylation was detected in brains from bird embryos suggesting that GSK-3 isozymes play distinct roles in tau phosphorylation during development. Birds are natural GSK-3α knockout organisms and may serve as a novel model to study the distinct functions of GSK-3 isozymes.
authors.affiliation: Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
authors.forename: Lina Tsaadon
authors.initials: LT
authors.lastname: Alon
authors.forename: Shmuel
authors.initials: S
authors.lastname: Pietrokovski
authors.forename: Shay
authors.initials: S
authors.lastname: Barkan
authors.forename: Limor
authors.initials: L
authors.lastname: Avrahami
authors.forename: Oksana
authors.initials: O
authors.lastname: Kaidanovich-Beilin
authors.forename: James R
authors.initials: JR
authors.lastname: Woodgett
authors.forename: Anat
authors.initials: A
authors.lastname: Barnea
authors.forename: Hagit
authors.initials: H
authors.lastname: Eldar-Finkelman
mesh_terms: D000818:Animals; D001717:Birds / Q000378:metabolism*; D015153:Blotting, Western; D001921:Brain / Q000196:embryology / Q000201:enzymology; D002642:Chick Embryo; D046369:Finches / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D006321:Heart / Q000196:embryology; D006801:Humans; D008099:Liver / Q000196:embryology / Q000201:enzymology; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D009206:Myocardium / Q000201:enzymology; D010766:Phosphorylation; D010802:Phylogeny; D046370:Sparrows / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D016875:tau Proteins; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D038362:Glycogen Synthase Kinase 3; C448021:glycogen synthase kinase 3 alpha