Interactomes of Glycogen Synthase Kinase-3 Isoforms

Area of Science:

• Molecular Biology
• Biochemistry
• Cell Biology

Background:

• Glycogen synthase kinase-3 (GSK-3) exists as two highly similar isoforms, GSK-3α and GSK-3β.
• Despite structural similarities, evidence suggests distinct functional roles and regulation for each GSK-3 isoform.
• Understanding isoform-specific interactions is crucial for elucidating functional differences.

Purpose of the Study:

• To identify novel protein interactors of GSK-3 isoforms.
• To compare the interactomes of GSK-3α and GSK-3β.
• To uncover isoform-specific protein interactions that may explain functional divergence.

Main Methods:

• Affinity purification coupled with mass spectrometry.
• Proximity-dependent biotinylation (BioID) followed by mass spectrometry.
• Validation of specific isoform-prey interactions.

Main Results:

• GSK-3α and GSK-3β interactomes were largely similar in HEK293 cells.
• BioID in HeLa cells revealed isoform-preferential interactors.
• DCP1B was identified as a GSK-3α-preferential interactor, and MISP as a GSK-3β-preferential interactor.

Conclusions:

• Isoform-specific protein interactions exist for GSK-3, particularly evident in HeLa cells.
• These distinct interactions provide a basis for understanding the specific functions of GSK-3α and GSK-3β.
• The findings open avenues for developing isoform-selective therapeutic strategies targeting GSK-3.