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

Research output: Contribution to journalArticlepeer-review


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 languageEnglish
Pages (from-to)1158-1162
Number of pages5
JournalFEBS Letters
Issue number8
StatePublished - 20 Apr 2011
Externally publishedYes

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.


  • Bird
  • Brain
  • Evolution
  • GSK-3
  • Tau phosphorylation


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