Selective loss of glycogen synthase kinase-3α in birds reveals distinct roles for GSK-3 isozymes in tau phosphorylation

Lina Tsaadon Alon; Shmuel Pietrokovski; Shay Barkan; Limor Avrahami; Oksana Kaidanovich-Beilin; James R. Woodgett; Anat Barnea; Hagit Eldar-Finkelman

doi:10.1016/j.febslet.2011.03.025

Selective loss of glycogen synthase kinase-3α in birds reveals distinct roles for GSK-3 isozymes in tau phosphorylation

Lina Tsaadon Alon, Shmuel Pietrokovski, Shay Barkan, Limor Avrahami, Oksana Kaidanovich-Beilin, James R. Woodgett, Anat Barnea, Hagit Eldar-Finkelman

Life Sciences discipline

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	1158-1162
Number of pages	5
Journal	FEBS Letters
Volume	585
Issue number	8
DOIs	https://doi.org/10.1016/j.febslet.2011.03.025
State	Published - 20 Apr 2011

Bibliographical note

Funding Information:
This work was supported by FP7 EU Grant #223276 “NeuroGSK3” and the Israeli Academy of Sciences , Grant #341/10 . JR Woodgett acknowledge Grant CIHR MOP#74711. We thank Dr. Tal Pupko for helpful discussions. We apologize to investigators whose work could not be cited because of space limitations.

Keywords

Bird
Brain
Evolution
GSK-3
Tau phosphorylation

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10.1016/j.febslet.2011.03.025

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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.",

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note = "Funding Information: This work was supported by FP7 EU Grant #223276 “NeuroGSK3” and the Israeli Academy of Sciences , Grant #341/10 . JR Woodgett acknowledge Grant CIHR MOP#74711. We thank Dr. Tal Pupko for helpful discussions. We apologize to investigators whose work could not be cited because of space limitations. ",

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AU - Kaidanovich-Beilin, Oksana

AU - Woodgett, James R.

AU - Barnea, Anat

AU - Eldar-Finkelman, Hagit

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Selective loss of glycogen synthase kinase-3α in birds reveals distinct roles for GSK-3 isozymes in tau phosphorylation

Abstract

Bibliographical note

Keywords

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