Chromogranin A: current status as a precursor for bioactive peptides and a granulogenic/sorting factor in the regulated secretory pathway

Iacangelo, Anna; Eiden, Lee E.

doi:10.1016/0167-0115(95)00069-n

Cited by 165 publications

(121 citation statements)

References 162 publications

(226 reference statements)

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confidence: 99%

“…These acidic secretory proteins play a role in the morphogenesis of secretory vesicles (Iacangelo and Eiden 1995;Kim et al 2001). There is also evidence that granins are precursor proteins that can be processed by prohormone convertases (PCs) to generate bioactive peptides (Simon and Aunis 1989;Winkler and Fischer-Colbrie 1992;Iacangelo and Eiden 1995). In particular, SgII is the precursor of a peptide named secretoneurin (SN) (Vaudry and Conlon 1991;Kirchmair et al 1993) which has been implicated in the modulation of the inflammatory response and may represent a novel sensory peptide for neuroimmunomodulation (Wiedermann 2000).…”

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confidence: 99%

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Biochemical Characterization and Immunocytochemical Localization of EM66, a Novel Peptide Derived from Secretogranin II, in the Rat Pituitary and Adrenal Glands

Montero-Hadjadje

Pelletier

Yon

et al. 2003

J Histochem Cytochem.

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(YT) S U M M A R Y Characterization of secretogranin II (SgII) mRNA in various vertebrates has revealed selective conservation of the amino acid sequences of two regions of the protein, i.e., the bioactive peptide secretoneurin and a flanking novel peptide that we named EM66. To help elucidate the possible role of EM66, we examined the occurrence as well as the cellular and subcellular distribution of EM66 in rat pituitary and adrenal glands by using a polyclonal antibody raised against the recombinant human EM66 peptide. High-performance liquid chromatography (HPLC) analysis of rat pituitary and adrenal extracts combined with a radioimmunoassay resolved EM66-immunoreactive material exhibiting the same retention time as recombinant EM66. In the rat pituitary, double-labeling immunohistochemical (IHC) studies showed that EM66 immunoreactivity (IR) was present in gonadotrophs, lactotrophs, thyrotrophs, and melanotrophs, whereas corticotrophs were devoid of labeling. EM66-IR was also observed in nerve endings in the neural lobe. Immunocytochemical staining at the electron microscopic level revealed that EM66-IR is sequestered in the secretory granules within gonadotrophs and lactotrophs. In the adrenal medulla, double IHC labeling showed that EM66-IR occurs exclusively in epinephrine-synthesizing cells. At the ultrastructural level, EM66-IR was seen in chromaffin vesicles of adrenomedullary cells. These results demonstrate that post-translational processing of SgII generates a novel peptide that exhibits a cell-specific distribution in the rat pituitary and adrenal glands where it is stored in secretory granules, supporting the notion that EM66 may play a role in the endocrine system.

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confidence: 99%

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confidence: 99%

Biochemical Characterization and Immunocytochemical Localization of EM66, a Novel Peptide Derived from Secretogranin II, in the Rat Pituitary and Adrenal Glands

Montero-Hadjadje

Pelletier

Yon

et al. 2003

J Histochem Cytochem.

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“…The secretory granules of endocrine cells, neurons, and neuroendocrine cells contain many hormones, ions, peptides and proteins, including 40 mM Ca 2ϩ and 1-2 mM chromogranins A and B in addition to high concentrations of hormones (1)(2)(3)(4)(5)(6). The secretory granule contents are secreted to the extracellular space and then into the bloodstream during exocytosis, which is initiated by a sudden increase of intracellular Ca 2ϩ concentration (7).…”

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confidence: 99%

“…Of the chromogranins, chromogranin A and chromogranin B are the two major proteins in virtually all secretory granules of endocrine cells, neurons, and neuroendocrine cells (1)(2)(3)(4)(5)(6). For instance, CGA is the most abundant protein in the bovine adrenal medullary chromaffin cells (1)(2)(3)(4)(5)(6), whereas CGB is the most abundant protein in human adrenal medullary chromaffin cells (35,36). Further, CGA is known to bind 55 mol of Ca 2ϩ /mol with a K d of 4 mM at the intragranular pH 5.5 and 32 mol of Ca 2ϩ /mol with a dissociation constant (K d ) of 2.7 mM at a near physiological pH 7.5 (37).…”

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confidence: 99%

Localization of Three Types of the Inositol 1,4,5-Trisphosphate Receptor/Ca2+ Channel in the Secretory Granules and Coupling with the Ca2+ Storage Proteins Chromogranins A and B

Yoo

Kang

et al. 2001

Journal of Biological Chemistry

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Although the role of secretory granules as the inositol 1,4,5-trisphosphate (IP 3 )-sensitive intracellular Ca 2؉ store and the presence of the IP 3 receptor (IP 3 R)/Ca 2؉ channel on the secretory granule membrane have been established, the identity of the IP 3 R types present in the secretory granules is not known. We have therefore investigated the presence of different types of IP 3 R in the secretory granules of bovine adrenal medullary chromaffin cells using immunogold electron microscopy and found the existence of all three types of IP 3 R in the secretory granules. To determine whether these IP 3 Rs interact with CGA and CGB, each IP 3 R isoform was cotransfected with CGA or CGB into NIH3T3 or COS-7 cells, and the expressed IP 3 R isoform and CGA or CGB were co-immunoprecipitated. From these studies it was shown that all three types of IP 3 R form complexes with CGA and CGB in the cells. To further confirm whether the IP 3 R isoforms and CGA and CGB form a complex in the secretory granules the potential interaction between all three isoforms of IP 3 R and CGA and CGB was tested by co-immunoprecipitation experiements of the mixture of secretory granule lysates and the granule membrane proteins. The three isoforms of IP 3 R were shown to form complexes with CGA and CGB, indicating the complex formation between the three isoforms of IP 3 R and CGA and CGB in the secretory granules. Moreover, the pH-dependent Ca 2؉ binding property of CGB was also studied using purified recombinant CGB, and it was shown that CGB bound 93 mol of Ca 2؉ /mol with a dissociation constant (K d ) of 1.5 mM at pH 5.5 but virtually no Ca 2؉ at pH 7.5. The high capacity, low affinity Ca 2؉ -binding property of CGB at pH 5.5 is comparable with that of CGA and is in line with its role as a Ca 2؉ storage protein in the secretory granules.The secretory granules of endocrine cells, neurons, and neuroendocrine cells contain many hormones, ions, peptides and proteins, including 40 mM Ca 2ϩ and 1-2 mM chromogranins A and B in addition to high concentrations of hormones (1-6). The secretory granule contents are secreted to the extracellular space and then into the bloodstream during exocytosis, which is initiated by a sudden increase of intracellular Ca 2ϩ concentration (7). In bovine adrenal medullary chromaffin cells the secretory granules occupy ϳ10% of the total cell volume (8), thereby storing a majority of the intracellular Ca 2ϩ of the cell in the secretory granules. Hence it appears inevitable for the secretory granules to participate in the control of intracellular Ca 2ϩ concentrations. Consistent with this notion, the secretory granules from adrenal medullary chromaffin cells (9), pancreatic acinar cells (10), and the goblet cells (11) concentrations but also in exocytotic processes. Despite the importance of the IP 3 -sensitive intracellular Ca 2ϩ store role of secretory granules, the study of IP 3 R/Ca 2ϩ channels in the secretory granules did not begin until the secretory granule Ca 2ϩ storage protein chromogranin A was shown to...

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“…Granins are characterized by their high content of acidic amino acids, their localization in secretory organelles of endocrine cells and neurons, and the presence in their sequences of multiple pairs of basic residues which represent potential cleavage sites for processing enzymes [2,3].…”

Section: Introductionmentioning

confidence: 99%

Molecular cloning of frog secretogranin II reveals the occurrence of several highly conserved potential regulatory peptides

et al. 1996

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Secretogranin II (Sgll) is an acidic secretory protein present in large dense core vesicles of neuronal and endocrine cells. Based on the sequence of a peptide derived from the processing of SgII in the brain of the frog Rana ridibunda, degenerate oligonucleotides were used to clone the cDNA encoding frog SgII from a pituitary cDNA library. This cDNA encodes a 574 amino acid protein which exhibits 46-48% sequence identity with mammalian SglI and contains 11 pairs of basic amino acids. Four potential processing products delimited by pairs of basic residues exhibited a much higher degree of identity (68--82%) with the corresponding mammalian SgII sequences. The frog SgII mRNA is ,--4 kb in length and is differentially expressed in the brain and endocrine tissues. The present data reveal that several SgII-derived peptides have been highly conserved during evolution, suggesting that these peptides may play important neuroendoerine regulatory functions.

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Chromogranin A: current status as a precursor for bioactive peptides and a granulogenic/sorting factor in the regulated secretory pathway

Cited by 165 publications

References 162 publications

Biochemical Characterization and Immunocytochemical Localization of EM66, a Novel Peptide Derived from Secretogranin II, in the Rat Pituitary and Adrenal Glands

Biochemical Characterization and Immunocytochemical Localization of EM66, a Novel Peptide Derived from Secretogranin II, in the Rat Pituitary and Adrenal Glands

Localization of Three Types of the Inositol 1,4,5-Trisphosphate Receptor/Ca2+ Channel in the Secretory Granules and Coupling with the Ca2+ Storage Proteins Chromogranins A and B

Molecular cloning of frog secretogranin II reveals the occurrence of several highly conserved potential regulatory peptides

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