Kibra Anchoring the Action of PKMζ Maintains the Persistence of Memory

Authors

Panayiotis Tsokas
Changchi Hsieh
Rafael E Flores-Obando
Matteo Bernabo
Andrew Tcherepanov
A Iván Hernández
Christian Thomas
Peter J Bergold
James E Cottrell
Joachim Kremerskothen
Harel Z Shouval
Karim Nader
André A Fenton
Todd C Sacktor

Publication Date

6-28-2024

Journal

Science Advances

Abstract

How can short-lived molecules selectively maintain the potentiation of activated synapses to sustain long-term memory? Here, we find kidney and brain expressed adaptor protein (KIBRA), a postsynaptic scaffolding protein genetically linked to human memory performance, complexes with protein kinase Mzeta (PKMζ), anchoring the kinase's potentiating action to maintain late-phase long-term potentiation (late-LTP) at activated synapses. Two structurally distinct antagonists of KIBRA-PKMζ dimerization disrupt established late-LTP and long-term spatial memory, yet neither measurably affects basal synaptic transmission. Neither antagonist affects PKMζ-independent LTP or memory that are maintained by compensating PKCs in ζ-knockout mice; thus, both agents require PKMζ for their effect. KIBRA-PKMζ complexes maintain 1-month-old memory despite PKMζ turnover. Therefore, it is not PKMζ alone, nor KIBRA alone, but the continual interaction between the two that maintains late-LTP and long-term memory.

Keywords

Animals, Protein Kinase C, Long-Term Potentiation, Mice, Mice, Knockout, Humans, Intracellular Signaling Peptides and Proteins, Memory, Memory, Long-Term, Synapses, Protein Binding, Phosphoproteins

DOI

10.1126/sciadv.adl0030

PMID

38924398

PMCID

PMC11204205

PubMedCentral® Posted Date

June 2024

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes