| CaMKIIα Protein | |
|---|---|
| Symbol | CAMK2A |
| Full Name | Calcium/Calmodulin-Dependent Protein Kinase II Alpha |
| UniProt ID | [Q9UQM7](https://www.uniprot.org/uniprot/Q9UQM7) |
| Molecular Weight | 54.1 kDa (monomer) |
| Subcellular Location | Cytoplasm, synapse, nucleus |
| PDB Structures | 3SOA, 5U6Y, 6BDQ |
Calcium/Calmodulin-Dependent Protein Kinase II alpha (CaMKIIα) is a serine/threonine kinase that serves as a central mediator of synaptic plasticity, learning, and memory. CaMKII is unique among kinases in its ability to become autonomously active after transient calcium stimulation, allowing it to function as a molecular memory switch at synapses.[1]
CaMKIIα forms large holoenzyme assemblies:
CaMKII is essential for long-term potentiation (LTP):
CaMKII serves as a memory trace molecule:
CaMKII function is disrupted in AD:
CaMKII contributes to excitotoxic neuronal death:
CaMKII dysfunction in HD:
CaMKII mediates ischemic damage:
Challenges in CaMKII targeting:
Investigational Compounds:
Lisman et al. CaMKII function in the synapse (2012). 2012. ↩︎
Coultrap & Bayer, CaMKII in neurodegeneration (2012). 2012. ↩︎
Yamauchi et al. Neuronal CaMKII structure and function (2005). 2005. ↩︎
Sanhueza M, et al. Role of the CaMKIIα/β complex in hippocampal synaptic plasticity. Neurobiol Learn Mem. 2011. ↩︎
Gu Z, et al. Aβ-dependent NMDA receptor endocytosis mediates synaptic loss during early Alzheimer's disease. J Neurosci. 2009. ↩︎
Zeng H, et al. Forebrain-specific calcineurin knockout selectively impairs bidirectional synaptic plasticity and working/episodic-like memory. Cell. 2001. ↩︎
Vest RS, et al. Dual mechanism of a novel CaMKII inhibitor. J Biol Chem. 2010. ↩︎
Cohen RM, et al. Excitotoxic lesions of the hippocampus impair spatial memory in CaMKIIα mutants. Neurobiol Learn Mem. 2008. ↩︎
Waxham MN, et al. CaMKII in cerebral ischemia. Neurosci Lett. 2020. ↩︎
Bayer KU, et al. Binding of autophosphorylated CaMKII to the NMDA receptor is independent of the CaMKII isoform. Biochem J. 2005. ↩︎
Coultrap SJ, et al. CaMKII inhibition in neurons: novel strategies and clinical implications. Neuropharmacology. 2019. ↩︎