Neurogranin
From Wikipedia, the free encyclopedia
Neurogranin is a calmodulin-binding protein expressed primarily in the brain, particularly in dendritic spines, and participating in the protein kinase C signaling pathway. Neurogranin has also been identified in aortic endothelial cells and cardiomyocytes.[5][6] It is the main postsynaptic protein regulating the availability of calmodulin by binding to it in the absence of calcium.
| NRGN | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Aliases | NRGN, RC3, hng, neurogranin | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | OMIM: 602350; MGI: 1927184; GeneCards: NRGN | |||||||||||||||||||||||||||||||||||||||||||||||||||||
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History
Structure
Human neurogranin is a small protein consisting of 78 amino acids.[8] Neurogranin belongs to a family of neuron-enriched calmodulin-binding proteins, together with neuromodulin (GAP-43), sharing a conserved central motif that functions both as the protein kinase C phosphorylation site and the calmodulin-binding domain.[7]
The protein contains an IQ motif (consensus sequence IQXXXRGXXXR), a characteristic sequence found in several calmodulin-binding proteins that mediates preferential binding to apo-calmodulin (calcium-free calmodulin). Phosphorylation of this region by protein kinase C reduces the affinity of neurogranin for calmodulin and modulates its signaling properties.[7]
Function
Neurogranin regulates intracellular calmodulin availability and functions as a key component of protein kinase C signaling. It preferentially binds calmodulin in the absence of calcium, whereas phosphorylation by protein kinase C reduces its calmodulin-binding capacity.
Expression of the NRGN gene is regulated by thyroid hormones through a thyroid hormone-responsive element located in the first intron.[9]
Recent studies suggest that neurogranin also contributes to cardiovascular physiology. In cardiomyocytes it regulates calcium-dependent cardiac hypertrophy,[10] and in endothelial cells it influences mitochondrial function and redox balance.[11]
Clinical significance
Genetic and neuropathological evidence has implicated neurogranin in schizophrenia. One study reported an association between variation in the NRGN gene and increased risk of schizophrenia in males,[12] while another demonstrated reduced neurogranin immunoreactivity in the prefrontal cortex of affected individuals.[13]
Neurogranin concentration in cerebrospinal fluid (CSF) has been investigated as a marker of synaptic dysfunction in age-related neurodegeneration.[14] CSF neurogranin has been shown to be increased in patients with Alzheimer's disease.[15][16] In particular, the ratio of CSF neurogranin truncated at P75 to the beta-secretase BACE1 has been proposed as a potential marker of cognitive deterioration during progression of Alzheimer's disease.[17]