Protein kinases: which one is the memory molecule?

J Micheau, G Riedel

Research output: Contribution to journalLiterature review

122 Citations (Scopus)

Abstract

Encoding of new experiences is likely to induce activity-dependent modifications in the brain. Studies in organisms far apart on the phylogenetic scale have shown that similar, sometimes identical, signal transduction pathways subserve plasticity in neuronal systems, and they may play pivotal roles in the formation of long-term memories. It has become evident that phosphorylation/dephosphorylation reactions are critical for the initiation of cellular mechanisms that embody, retain and modify information in neural circuits. Although physiological investigations on synaptic plasticity have had a major impact, we have concentrated our review on behavioural studies that provide direct or indirect evidence for a role of kinases in mechanisms underlying memory formation. From these, it appears that the learning event induces activation of a variety of kinases with specific time courses. For instance, the calcium/calmodulin-dependent protein kinase II seems to participate in an early phase of memory formation. Apparently, activation of both protein tyrosine kinases and mitogen-activated protein kinases is required for much longer and may thus have a particular function during transformation from short-term into long-term memory. Quite different time courses appear for protein kinase C (PKC) and protein kinase A (PKA), which may function at two different time points, shortly after training and again much later. This suggests that PKC and PKA might play a role at early and late stages of memory formation. However, we have considered some examples showing that these signalling pathways do not function in isolation but rather interact in an intricate intracellular network. This is indicative of a more complex contribution of each kinase to the fine tuning of encoding and information processing. To decipher this complexity, pharmacological, biochemical and genetic investigations are more than ever necessary to unravel the role of each kinase in the syntax of learning and memory formation.

Original languageEnglish
Pages (from-to)534-548
Number of pages15
JournalCellular and Molecular Life Sciences
Volume55
Publication statusPublished - 1999

Keywords

  • memory cellular mechanisms
  • signalling pathways
  • protein kinases
  • PKC
  • PKA
  • CaMKII
  • MAPK and PTK
  • LONG-TERM POTENTIATION
  • DAY-OLD CHICKS
  • APLYSIA SENSORY NEURONS
  • DEPENDENT LATE-PHASE
  • GAMMA-MUTANT MICE
  • MAP KINASE
  • TYROSINE PHOSPHORYLATION
  • SIGNALING PATHWAY
  • II ACTIVITY
  • SYNAPTIC TRANSMISSION

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