Brain Molecular Pathways
Brain Molecular Pathways Brain Molecular Pathways
CaMKII -- Ca2+/calmodulin-dependent protein kinases II are serine/threonine-specific protein kinases that are regulated by the calmodulin complex. CaMKII phosphorylates AMPA receptors at the P2 serine 831 site. This increases channel conductance of GluA1 subunits of AMPA receptors.
1. concentration of cAMP rises (e.g., activation of adenylate cyclase via GPCR-Gs)
2. cAMP molecules bind and release each PKA regulatory subunit.
3. catalytic subunits phosphorylate Ser and Thr residues
4. PKA can directly activate CREB, which binds CRE, altering the transcription
Arc, for activity-regulated cytoskeleton-associated protein (also known as Arg3.1), is a plasticity protein first characterized in 1995. Arc is a member of the immediate-early gene (IEG) family, a rapidly activated class of genes functionally defined by their ability to be transcribed in the presence of protein synthesis inhibitors. Arc mRNA is localized to activated synaptic sites in an NMDA receptor-dependent manner, where the newly translated protein is believed to play a critical role in learning and memory-related molecular processes. Arc is widely considered to be an important protein in neurobiology because of its activity regulation, localization, and utility as a marker for plastic changes in the brain. Along with other IEGs such as zif268 and Homer 1a, Arc is also a significant tool for systems neuroscience as illustrated by the development of the cellular compartment analysis of temporal activity by fluorescence in situ hybridization, or catFISH technique (see fluorescent in situ hybridization).
Cyclic AMP or cAMP works by activating protein kinase A (PKA, cAMP-dependent protein kinase). PKA is normally inactive as a tetrameric holoenzyme, consisting of two catalytic and two regulatory units (C2R2), with the regulatory units blocking the catalytic centers of the catalytic units. Cyclic AMP binds to specific locations on the regulatory units of the protein kinase, and causes dissociation between the regulatory and catalytic subunits, thus activating the catalytic units and enabling them to phosphorylate substrate proteins. There are some minor PKA-independent functions of cAMP, e.g., activation of calcium channels, providing a minor pathway by which growth hormone-releasing hormone causes a release of growth hormone.