Alpha-isoform of Ca2+/calmodulin-dependent kinase II autophosphorylation is required for memory consolidation-specific transcription

Abstract

Autophosphorylation of the alpha-isoform of Ca2+/calmodulin-dependent kinase II switches the kinase into an autonomous activity mode. This molecular switch is important for hippocampal long-term memory formation, which requires de novo gene transcription and protein synthesis. Here, we have studied whether auto-phosphorylation of the alpha-isoform of Ca2+/calmodulin-dependent kinase II is required for gene transcription induced in the hippocampus by contextual fear conditioning. We have shown that upregulation of a nonassociative transcript, the serum and glucocorticoid-induced kinase-1 messenger RNA, is normal in alpha-isoform of Ca2+/calmodulin-dependent kinase II autophosphorylation-deficient mutant mice, whereas upregulation of an associative transcript, the nerve growth factor-inducible gene B messenger RNA, is impaired. Thus, we suggest that autophosphorylation of the alpha-isoform of Ca2+/calmodulin-dependent kinase II is a biochemical switch that regulates association-specific consolidation processes.

Protein degradation and protein synthesis in long-term memory formation

“…One such signaling molecule is CaMKII which is thought to be involved in changes in gene transcription and protein synthesis through its regulation of CREB (Wayman et al, 2008), a critical regulator of LTM formation and stability in the neurons (Josselyn et al, 2001; Han et al, 2007, 2008, 2009). Indeed, numerous studies have suggested that CaMKII is critical for LTM formation and that this requirement for CaMKII signaling overlaps with the requirement for protein degradation and synthesis during memory consolidation (Barros et al, 1999; Rodrigues et al, 2004; Von Hertzen and Giese, 2005; Halt et al, 2012; Da Silva et al, 2013). Collectively, these results suggest that changes in NMDAR and CaMKII activity correlate with changes in both protein degradation and protein synthesis during LTM formation in neurons.…”

Regulation of CaMKII In vivo: The Importance of Targeting and the Intracellular Microenvironment

“…One or more members of this family are found in virtually every tissue, and mediate diverse physiological responses triggered by increases in intracellular calcium concentrations, activation by the binding of calcium/calmodulin and the ability to undergo autophosphorylation. CaMKII is expressed most abundantly in neurons, and is involved in regulating many aspects of neuronal function, including neurotransmitter synthesis and release, modulation of ion channel activity, cellular transport, cellular morphology and neurite extension, long-term plasticity, learning, memory consolidation, and memory erasure following retrieval [2][3][4][5][6][7]. Non-neuronal CaMKII has been implicated in the regulation of other biological processes, such as fertilisation [8], osteogenic differentiation [9], and the maintenance of vascular tone [10].…”

Ca2+/Calmodulin Kinase Kinase α Is Dispensable for Brain Development but Is Required for Distinct Memories in Male, though Not in Female, Mice

“…Up-regulation of hippocampal NGFI-B mRNA expression after contextual fear conditioning is independent of sex and is not impaired in Camkk1 hypomorphic mutants. Like BDNF, nerve growth factor-inducible gene B is a CREB target gene and its hippocampal mRNA expression is up-regulated specifically by the learned association after contextual fear conditioning (50,51). We studied whether the up-regulation of hippocampal NGFI-B mRNA expression after contextual fear conditioning is also dependent on sex and whether it requires CaMKK␣ signaling (Fig.…”