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PKMζ-KIBRA interactions, molecular turnover, and memory.
Changchi Hsieh1, David A Cano2, Panayiotis Tsokas1,3,4
1Department of Physiology and Pharmacology, The Robert F. Furchgott Center for Neural and Behavioral Science, State University of New York Downstate Health Sciences University, Brooklyn, NY, 11203, USA.
Molecular Brain
|March 12, 2026
Summary
Persistent KIBRA-PKMζ oligomers maintain long-term memory by overcoming molecular turnover. Continuous formation of these molecular structures ensures memory consolidation despite the degradation of individual protein components.
Area of Science:
- Neuroscience
- Molecular Biology
- Structural Biology
Background:
- Persistent interaction between KIBRA and PKMζ is vital for maintaining synaptic plasticity and long-term memory.
- Molecular turnover of KIBRA and PKMζ poses a challenge to memory persistence beyond their individual lifespans.
Purpose of the Study:
- To investigate the structural basis of KIBRA-PKMζ interaction and its role in overcoming molecular turnover for memory maintenance.
- To elucidate how KIBRA-PKMζ oligomers facilitate continuous memory consolidation.
Main Methods:
- Utilized AlphaFold 3 to predict the structures of KIBRA-PKMζ heterodimers and heterohexamers.
- Examined the mechanism of action of KIBRA-PKMζ interaction inhibitors (K-ZAP and ζ-stat).
- Assessed the impact of inhibitors on established late-LTP and long-term spatial memory.
Main Results:
- Predicted structures revealed K-ZAP blocks heterodimer formation and ζ-stat prevents the assembly of larger oligomeric structures.
- Both K-ZAP and ζ-stat disrupted 1-month-old spatial memory, indicating the importance of oligomer formation.
- Continuous KIBRA-PKMζ oligomerization is essential for overcoming molecular turnover and sustaining memory.
Conclusions:
- Continuous formation of KIBRA-PKMζ oligomers is a fundamental molecular mechanism for long-term memory persistence.
- Structural insights into KIBRA-PKMζ interactions provide a basis for understanding memory consolidation and potential therapeutic targets.
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