Neurogranin: Proteins and Enzymes

Neurogranin, also known as RC3, p17, and BICKS (B-50 Immunoreactive C-Kinase Substrate), is a member of the neurogranin family of proteins. Human Neurogranin is 78 amino acids (aa) in length with a predicted molecular weight of 7.5 kDa. It shares 96% aa sequence identity with the mouse and rat orthologs.

Neurogranin is a postsynaptic protein involved in regulating synaptic plasticity. It is primarily expressed in the brain, specifically in Golgi and Purkinje cells of the cerebellum and excitatory neurons in the telencephalon. It is the most abundant postsynaptic Calmodulin (CaM)-binding protein and is important for LTP and NMDA receptor-induced increases in synaptic strength. Neurogranin regulates synaptic plasticity by controlling the levels of free CaM. Neurogranin binds to CaM via its IQ domain (aa 26-47).

Increases in intracellular calcium and PKC-mediated phosphorylation of Neurogranin at serine 36 initiates CaM release. CaM then binds to calcium and activates calcium/CaM-dependent enzymes, such as CaM Kinase II. Neurogranin has been proposed to be a cerebrospinal fluid (CSF) biomarker for Alzheimer’s disease (AD). Studies have shown that Neurogranin levels in CSF are higher in patients with AD compared to cognitively normal individuals. Researchers have suggested that the elevated levels of Neurogranin in the CSF reflect synaptic dysfunction or degeneration occurring in AD.

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