Ca2+/calmodulin-dependent protein kinase II
Ca2+/calmodulin-dependent protein kinase II (CaMKII) is a serine/threonine-specific protein kinase that is regulated by the [[Ca2+]]/calmodulin complex. CaMKII is involved in many signaling cascades and is thought to be an important mediator of learning and memory. This enzyme is ubiquitous in eukaryotic cells and is especially abundant in neurons. It is also involved in other cellular processes such as cell cycle regulation, apoptosis, and cytoskeletal rearrangement.
Structure[edit | edit source]
CaMKII is a multimeric enzyme, typically composed of 12 to 14 subunits, which are organized in a dodecameric structure. Each subunit can bind to calmodulin, a small protein that can bind calcium ions (Ca2+), leading to the activation of the kinase activity of CaMKII. The enzyme has a regulatory domain that inhibits kinase activity; binding of Ca2+/calmodulin relieves this inhibition, leading to activation of the enzyme.
Function[edit | edit source]
The primary function of CaMKII is the phosphorylation of serine or threonine residues in target proteins. This phosphorylation can change the activity of the target protein, leading to a cellular response. In neurons, CaMKII is involved in the regulation of synaptic plasticity, a cellular mechanism for learning and memory. CaMKII phosphorylates various proteins involved in the regulation of synaptic strength, including receptors and ion channels.
CaMKII also plays a role in the regulation of gene expression by phosphorylating transcription factors, which can lead to changes in gene expression patterns necessary for long-term memory formation.
Regulation[edit | edit source]
The activity of CaMKII is regulated by several mechanisms. The most important is the binding of Ca2+/calmodulin, which leads to enzyme activation. Additionally, CaMKII can undergo autophosphorylation, which can lead to a state of autonomous activity even after the Ca2+ levels have fallen and calmodulin has dissociated. This autophosphorylation is thought to be important for the role of CaMKII in memory consolidation.
Clinical Significance[edit | edit source]
Alterations in CaMKII function have been implicated in a variety of diseases, including cardiac hypertrophy, arrhythmias, and neurodegenerative diseases such as Alzheimer's disease. Given its role in synaptic plasticity, CaMKII is also being studied for its potential role in psychiatric disorders, including schizophrenia and depression.
Research[edit | edit source]
Research on CaMKII continues to uncover its roles in various cellular processes and diseases. Understanding the precise mechanisms by which CaMKII influences cellular function and how its activity is regulated may lead to the development of new therapeutic strategies for diseases associated with its dysregulation.
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Contributors: Prab R. Tumpati, MD