Calmodulin acetylation: A modification to remember

Abstract

The formation of new memories appears to require alterations in the shape and strength of synapses within the hippocampus, yet our knowledge of the molecular mechanisms underlying these changes remains incomplete. Zhang and colleagues provide new understanding of memory formation by uncovering the lysine acetyltransferase SRC3 as the key driver of the novel posttranslational modification of calmodulin (CaM) acetylation, which regulates CaM's activity and subsequent activation of CaMKII. This new pathway is demonstrated to be both necessary and sufficient for CA3→CA1 synapse long-term potentiation (LTP) and fear memory formation, and this approach may act as a blueprint for future investigation of the role of acetylation of other proteins in neuronal functions.

Figure 1

A novel mechanism for synaptic plasticity.A, schematic depicting location of dorsal hippocampus in mouse brain (left) and a CA3→CA1 synapse within the hippocampus (right). B, within the CA1 postsynaptic element, NMDA receptors activated by glutamate allow influx of Ca²⁺, which drives the acetylation (Ac) of CaM by SRC3. Ac-CaM bound to Ca²⁺ causes CaMKIIα activation and autophosphorylation (P), driving AMPA receptors to the synapse and increasing their phosphorylation (P), key steps in long-term potentiation (LTP).