Neurogranin Explained

neurogranin (protein kinase C substrate, RC3)
Hgncid:8000
Symbol:NRGN
Entrezgene:4900
Omim:602350
Refseq:NM_006176
Uniprot:Q92686
Chromosome:11
Arm:q
Band:24

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 recently been found in aortic endothelial cells and cardiomyocytes.[1] [2] Neurogranin is the main postsynaptic protein regulating the availability of calmodulin, binding to it in the absence of calcium. Phosphorylation by protein kinase C lowers its binding ability. NRGN gene expression is controlled by thyroid hormones.[3] Human neurogranin consists of 78 amino acids.

One study tells of potential link of neurogranin gene to the heightened risk of schizophrenia in males,[4] another study gives evidence of lowered neurogranin immunoreactivity in the brains of people suffering from schizophrenia.[5]

Neurogranin concentration in cerebrospinal fluid (CSF) is further discussed as marker for synaptic dysfunction in age-related neurodegeneration.[6] It has also been shown to be specifically increased in patients with Alzheimer's disease.[7] [8] Especially, the ratio of CSF neurogranin trunc P75 and the beta-secretase BACE1 is suggested as a potential marker for cognitive deterioration in the progress of Alzheimer's disease.[9]

Prior to its identification in the bovine and rat brain in 1991,[10] neurogranin was known as a putative protein kinase C-phosphorylated protein named p17. Human neurogranin was cloned in 1997 and turned out to be 96% identical to the rat protein.[11]

Notes and References

  1. Jorgensen . Ashton N. . Abdullah . Chowdhury S. . Bhuiyan . Md. Shenuarin . Watt . Megan . Dominic . Paari . Kolluru . Gopi K. . Kevil . Christopher G. . Nam . Hyung W. . Neurogranin regulates calcium-dependent cardiac hypertrophy . Experimental and Molecular Pathology . August 2022 . 127 . 104815 . 10.1016/j.yexmp.2022.104815 . 35870494 . 250941689 . 11118017 .
  2. Jorgensen . Ashton N. . Rashdan . Nabil A. . Rao . K.N. Shashanka . Delgadillo . Luisa F. . Kolluru . Gopi K. . Krzywanski . David M. . Pattillo . Christopher B. . Kevil . Christopher G. . Nam . Hyung W. . Neurogranin expression regulates mitochondrial function and redox balance in endothelial cells . Redox Biology . April 2024 . 70 . 103085 . 10.1016/j.redox.2024.103085 . 38359746 . 10878108 .
  3. Martínez de Arrieta C, Morte B, Coloma A, Bernal J . The human RC3 gene homolog, NRGN contains a thyroid hormone-responsive element located in the first intron . Endocrinology . 140 . 1 . 335–43 . January 1999 . 9886843 . 10.1210/en.140.1.335 . free . 10261/24257 . free .
  4. Ruano D, Aulchenko YS, Macedo A, Soares MJ, Valente J, Azevedo MH, Hutz MH, Gama CS, Lobato MI, Belmonte-de-Abreu P, Goodman AB, Pato C, Heutink P, Palha JA . 6 . Association of the gene encoding neurogranin with schizophrenia in males . Journal of Psychiatric Research . 42 . 2 . 125–33 . January 2008 . 17140601 . 10.1016/j.jpsychires.2006.10.008 .
  5. Broadbelt K, Ramprasaud A, Jones LB . Evidence of altered neurogranin immunoreactivity in areas 9 and 32 of schizophrenic prefrontal cortex . Schizophrenia Research . 87 . 1–3 . 6–14 . October 2006 . 16797925 . 10.1016/j.schres.2006.04.028 . 38984915 .
  6. Casaletto KB, Elahi FM, Bettcher BM, Neuhaus J, Bendlin BB, Asthana S, Johnson SC, Yaffe K, Carlsson C, Blennow K, Zetterberg H, Kramer JH . 6 . Neurogranin, a synaptic protein, is associated with memory independent of Alzheimer biomarkers . Neurology . 89 . 17 . 1782–1788 . October 2017 . 28939668 . 5664306 . 10.1212/WNL.0000000000004569 .
  7. De Vos A, Jacobs D, Struyfs H, Fransen E, Andersson K, Portelius E, Andreasson U, De Surgeloose D, Hernalsteen D, Sleegers K, Robberecht C, Van Broeckhoven C, Zetterberg H, Blennow K, Engelborghs S, Vanmechelen E . 6 . C-terminal neurogranin is increased in cerebrospinal fluid but unchanged in plasma in Alzheimer's disease . Alzheimer's & Dementia . 11 . 12 . 1461–1469 . December 2015 . 26092348 . 10.1016/j.jalz.2015.05.012 . free .
  8. Willemse EA, De Vos A, Herries EM, Andreasson U, Engelborghs S, van der Flier WM, Scheltens P, Crimmins D, Ladenson JH, Vanmechelen E, Zetterberg H, Fagan AM, Blennow K, Bjerke M, Teunissen CE . 6 . Neurogranin as Cerebrospinal Fluid Biomarker for Alzheimer Disease: An Assay Comparison Study . Clinical Chemistry . 64 . 6 . 927–937 . June 2018 . 29523639 . 10.1373/clinchem.2017.283028 . free . 10067/1495100151162165141 . free .
  9. De Vos A, Struyfs H, Jacobs D, Fransen E, Klewansky T, De Roeck E, Robberecht C, Van Broeckhoven C, Duyckaerts C, Engelborghs S, Vanmechelen E . 6 . The Cerebrospinal Fluid Neurogranin/BACE1 Ratio is a Potential Correlate of Cognitive Decline in Alzheimer's Disease . Journal of Alzheimer's Disease . 53 . 4 . 1523–38 . July 2016 . 27392859 . 4981899 . 10.3233/JAD-160227 .
  10. Baudier J, Deloulme JC, Van Dorsselaer A, Black D, Matthes HW . Purification and characterization of a brain-specific protein kinase C substrate, neurogranin (p17). Identification of a consensus amino acid sequence between neurogranin and neuromodulin (GAP43) that corresponds to the protein kinase C phosphorylation site and the calmodulin-binding domain . The Journal of Biological Chemistry . 266 . 1 . 229–37 . January 1991 . 10.1016/S0021-9258(18)52425-X . 1824695 . free .
  11. Martínez de Arrieta C, Pérez Jurado L, Bernal J, Coloma A . Structure, organization, and chromosomal mapping of the human neurogranin gene (NRGN) . Genomics . 41 . 2 . 243–9 . April 1997 . 9143500 . 10.1006/geno.1997.4622 .

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