The Extended Granin Family: Structure, Function, and Biomedical Implications

Overview

Journal Endocr Rev

Publisher Oxford University Press

Specialty Endocrinology

Date 2011 Aug 25

PMID 21862681

Citations 165

Authors

Alessandro Bartolomucci

Roberta Possenti

Sushil K Mahata

Reiner Fischer-Colbrie

Y Peng Loh

Stephen R J Salton

Affiliations

Soon will be listed here.

Abstract

The chromogranins (chromogranin A and chromogranin B), secretogranins (secretogranin II and secretogranin III), and additional related proteins (7B2, NESP55, proSAAS, and VGF) that together comprise the granin family subserve essential roles in the regulated secretory pathway that is responsible for controlled delivery of peptides, hormones, neurotransmitters, and growth factors. Here we review the structure and function of granins and granin-derived peptides and expansive new genetic evidence, including recent single-nucleotide polymorphism mapping, genomic sequence comparisons, and analysis of transgenic and knockout mice, which together support an important and evolutionarily conserved role for these proteins in large dense-core vesicle biogenesis and regulated secretion. Recent data further indicate that their processed peptides function prominently in metabolic and glucose homeostasis, emotional behavior, pain pathways, and blood pressure modulation, suggesting future utility of granins and granin-derived peptides as novel disease biomarkers.

Citing Articles

Blockade of glucagon receptor induces α-cell hypersecretion by hyperaminoacidemia in mice.

Jia J, Bai X, Kang Q, Jiang F, Wong F, Jin Q Nat Commun. 2025; 16(1):2473.

PMID: 40075066 PMC: 11903786. DOI: 10.1038/s41467-025-57786-7.

Secretogranin III: a promising therapeutic target for intraocular neovascular lesions.

Yuan C, Zuo L, Dong Y, Liu B, Qi H Int Ophthalmol. 2025; 45(1):26.

PMID: 39832055 PMC: 11746947. DOI: 10.1007/s10792-024-03393-2.

Cocaine-Induced Remodeling of the Rat Brain Peptidome: Quantitative Mass Spectrometry Reveals Anatomically Specific Patterns of Cocaine-Regulated Peptide Changes.

Lu G, Ma F, Wei P, Ma M, Tran V, Baldo B ACS Chem Neurosci. 2025; 16(2):128-140.

PMID: 39810605 PMC: 11736046. DOI: 10.1021/acschemneuro.4c00327.

Dominant Expression of Chromogranin B in Pituitary Corticotrophs and Its Putative Role in Interaction With Secretogranin III.

Kikuchi S, Odashima K, Yasui T, Torii S, Hosaka M, Gomi H J Histochem Cytochem. 2025; 73(1-2):29-53.

PMID: 39791490 PMC: 11719422. DOI: 10.1369/00221554241311965.

An In Vivo Model of Estrogen Supplementation Concerning the Expression of Ca-Dependent Exchangers and Mortality, Vitality and Survival After Myocardial Infarction in Ovariectomized Rats.

Toporcer T, Grendel T, Spakova I, Blicharova A, Verboova L, Benetinova Z J Cardiovasc Dev Dis. 2024; 11(11).

PMID: 39590195 PMC: 11595027. DOI: 10.3390/jcdd11110352.

References

Wakonigg G, Zernig G, Berger I, Fischer-Colbrie R, Laslop A, Saria A . Lack of a distinctive behavioural effect of chromogranin-derived peptides in rodents. Regul Pept. 2002; 103(2-3):85-91. DOI: 10.1016/s0167-0115(01)00365-2. View

Wolkersdorfer M, Laslop A, Lazure C, Fischer-Colbrie R, Winkler H . Processing of chromogranins in chromaffin cell culture: effects of reserpine and alpha-methyl-p-tyrosine. Biochem J. 1996; 316 ( Pt 3):953-8. PMC: 1217441. DOI: 10.1042/bj3160953. View

Snyder S, Pintar J, Salton S . Developmental expression of VGF mRNA in the prenatal and postnatal rat. J Comp Neurol. 1998; 394(1):64-90. View

Jain R, Chang W, Geetha C, Joyce P, Gorr S . In vitro aggregation of the regulated secretory protein chromogranin A. Biochem J. 2002; 368(Pt 2):605-10. PMC: 1222998. DOI: 10.1042/BJ20021195. View

Heaney A, Curry W, Pogue K, Armstrong V, Mirakhur M, Sheridan B . Immunohistochemical evaluation of the post-translational processing of chromogranin A in human pituitary adenomas. Pituitary. 2001; 3(2):67-75. DOI: 10.1023/a:1009949623054. View

Kruger P, Mahata S, Helle K . Catestatin (CgA344-364) stimulates rat mast cell release of histamine in a manner comparable to mastoparan and other cationic charged neuropeptides. Regul Pept. 2003; 114(1):29-35. DOI: 10.1016/s0167-0115(03)00069-7. View

Stadinski B, Delong T, Reisdorph N, Reisdorph R, Powell R, Armstrong M . Chromogranin A is an autoantigen in type 1 diabetes. Nat Immunol. 2010; 11(3):225-31. PMC: 3166626. DOI: 10.1038/ni.1844. View

Zhao E, Basak A, Wong A, Ko W, Chen A, Lopez G . The secretogranin II-derived peptide secretoneurin stimulates luteinizing hormone secretion from gonadotrophs. Endocrinology. 2008; 150(5):2273-82. DOI: 10.1210/en.2008-1060. View

Greider M, Howell S, Lacy P . Isolation and properties of secretory granules from rat islets of Langerhans. II. Ultrastructure of the beta granule. J Cell Biol. 1969; 41(1):162-6. PMC: 2107726. DOI: 10.1083/jcb.41.1.162. View

10.

Kogner P, Bjellerup P, Svensson T, Theodorsson E . Pancreastatin immunoreactivity in favourable childhood neuroblastoma and ganglioneuroma. Eur J Cancer. 1995; 31A(4):557-60. DOI: 10.1016/0959-8049(95)00057-p. View

11.

Kirchmair R, Egger M, Walter D, Eisterer W, Niederwanger A, Woell E . Secretoneurin, an angiogenic neuropeptide, induces postnatal vasculogenesis. Circulation. 2004; 110(9):1121-7. DOI: 10.1161/01.CIR.0000139884.81390.56. View

12.

Qian Y, Devi L, Mzhavia N, Munzer S, Seidah N, Fricker L . The C-terminal region of proSAAS is a potent inhibitor of prohormone convertase 1. J Biol Chem. 2000; 275(31):23596-601. DOI: 10.1074/jbc.M001583200. View

13.

Sibilia V, Pagani F, Bulgarelli I, Mrak E, Broccardo M, Improta G . TLQP-21, a VGF-derived peptide, prevents ethanol-induced gastric lesions: insights into its mode of action. Neuroendocrinology. 2010; 92(3):189-97. DOI: 10.1159/000319791. View

14.

Montero-Hadjadje M, Vaingankar S, Elias S, Tostivint H, Mahata S, Anouar Y . Chromogranins A and B and secretogranin II: evolutionary and functional aspects. Acta Physiol (Oxf). 2007; 192(2):309-24. DOI: 10.1111/j.1748-1716.2007.01806.x. View

15.

Landen M, Davidsson P, Gottfries C, Grenfeldt B, Stridsberg M, Blennow K . Reduction of the small synaptic vesicle protein synaptophysin but not the large dense core chromogranins in the left thalamus of subjects with schizophrenia. Biol Psychiatry. 2000; 46(12):1698-702. DOI: 10.1016/s0006-3223(99)00160-2. View

16.

Succu S, Mascia M, Melis T, Sanna F, Melis M, Possenti R . Pro-VGF-derived peptides induce penile erection in male rats: Involvement of paraventricular nitric oxide. Neuropharmacology. 2005; 49(7):1017-25. DOI: 10.1016/j.neuropharm.2005.05.015. View

17.

Sanchez-Margalet V, Gonzalez-Yanes C, Najib S, Santos-Alvarez J . Metabolic effects and mechanism of action of the chromogranin A-derived peptide pancreastatin. Regul Pept. 2010; 161(1-3):8-14. DOI: 10.1016/j.regpep.2010.02.005. View

18.

Helle K . The chromogranins. Historical perspectives. Adv Exp Med Biol. 2001; 482:3-20. DOI: 10.1007/0-306-46837-9_1. View

19.

Omland T, Dickstein K, Syversen U . Association between plasma chromogranin A concentration and long-term mortality after myocardial infarction. Am J Med. 2003; 114(1):25-30. DOI: 10.1016/s0002-9343(02)01425-0. View

20.

Greenwood T, Cadman P, Stridsberg M, Nguyen S, Taupenot L, Schork N . Genome-wide linkage analysis of chromogranin B expression in the CEPH pedigrees: implications for exocytotic sympathochromaffin secretion in humans. Physiol Genomics. 2004; 18(1):119-27. DOI: 10.1152/physiolgenomics.00104.2003. View