Secretory granule protein chromogranin B (CHGB) forms an anion channel in membranes

Yadav, Gaya P.; Zheng, Hui; Yang, Qing; Douma, Lauren G.; Bloom, Linda B.; Jiang, Qiu‐Xing

doi:10.26508/lsa.201800139

Cited by 12 publications

(30 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Future study will be needed to identify the iTAFs as we did previously (see Ref. 65) and to verify their functions in both telomerase-positive and -negative cells.…”

Section: Itafs Differ From Other Proteinaceous Factors That Regulate mentioning

confidence: 88%

Catalysis-dependent inactivation of human telomerase and its reactivation by intracellular telomerase-activating factors (iTAFs)

Sayed

Cheng

Yadav

et al. 2019

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Edited by Xiao-Fan Wang Human telomerase maintains genome stability by adding telomeric repeats to the ends of linear chromosomes. Although previous studies have revealed profound insights into telomerase functions, the low cellular abundance of functional telomerase and the difficulties in quantifying its activity leave its thermodynamic and kinetic properties only partially characterized. Employing a stable cell line overexpressing both the human telomerase RNA component and the N-terminally biotinylated human telomerase reverse transcriptase and using a newly developed method to count individual extension products, we demonstrate here that human telomerase holoenzymes contain fast-and slow-acting catalytic sites. Surprisingly, both active sites became inactive after two consecutive rounds of catalysis, named single-run catalysis. The fast active sites turned off ϳ40fold quicker than the slow ones and exhibited higher affinities to DNA substrates. In a dimeric enzyme, the two active sites work in tandem, with the faster site functioning before the slower one, and in the monomeric enzyme, the active sites also perform single-run catalysis. Interestingly, inactive enzymes could be reactivated by intracellular telomerase-activating factors (iTAFs) from multiple cell types. We conclude that the single-run catalysis and the iTAFtriggered reactivation serve as an unprecedented control circuit for dynamic regulation of telomerase. They endow native telomerase holoenzymes with the ability to match their total number of active sites to the number of telomeres they extend. We propose that the exquisite kinetic control of telomerase activity may play important roles in both cell division and cell aging.

show abstract

“…Future study will be needed to identify the iTAFs as we did previously (see Ref. 65) and to verify their functions in both telomerase-positive and -negative cells.…”

Section: Itafs Differ From Other Proteinaceous Factors That Regulate mentioning

confidence: 88%

Catalysis-dependent inactivation of human telomerase and its reactivation by intracellular telomerase-activating factors (iTAFs)

Sayed

Cheng

Yadav

et al. 2019

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

show abstract

“…An increase in calcium in vascular smooth muscle cells leads to an augmented muscular tone which further increases vascular resistance that eventually raises the blood pressure [38]. One such gene is CHGB [39] that stimulates catecholamine secretion [40]. Common genetic variation at the CHGB locus, especially in the proximal promoter, influences CHGB expression, catecholamine secretion and the early heritable responses to environmental stress and is associated with changes in blood pressure in the sub-Saharan African and European ancestry groups [33].…”

Section: Discussionmentioning

confidence: 99%

Selected neuropeptide genes show genetic differentiation between Africans and non-Africans

et al. 2020

View full text Add to dashboard Cite

Background: Publicly available genome data provides valuable information on the genetic variation patterns across different modern human populations. Neuropeptide genes are crucial to the nervous, immune, endocrine system, and physiological homeostasis as they play an essential role in communicating information in neuronal functions. It remains unclear how evolutionary forces, such as natural selection and random genetic drift, have affected neuropeptide genes among human populations. To date, there are over 100 known human neuropeptides from the over 1000 predicted peptides encoded in the genome. The purpose of this study is to analyze and explore the genetic variation in continental human populations across all known neuropeptide genes by examining highly differentiated SNPs between African and non-African populations. Results: We identified a total of 644,225 SNPs in 131 neuropeptide genes in 6 worldwide population groups from a public database. Of these, 5163 SNPs that had ΔDAF |(African-non-African)| ≥ 0.20 were identified and fully annotated. A total of 20 outlier SNPs that included 19 missense SNPs with a moderate impact and one stop lost SNP with high impact, were identified in 16 neuropeptide genes. Our results indicate that an overall strong population differentiation was observed in the non-African populations that had a higher derived allele frequency for 15/20 of those SNPs. Highly differentiated SNPs in four genes were particularly striking: NPPA (rs5065) with high impact stop lost variant; CHGB (rs6085324, rs236150, rs236152, rs742710 and rs742711) with multiple moderate impact missense variants; IGF2 (rs10770125) and INS (rs3842753) with moderate impact missense variants that are in linkage disequilibrium. Phenotype and disease associations of these differentiated SNPs indicated their association with hypertension and diabetes and highlighted the pleiotropic effects of these neuropeptides and their role in maintaining physiological homeostasis in humans. Conclusions: We compiled a list of 131 human neuropeptide genes from multiple databases and literature survey. We detect significant population differentiation in the derived allele frequencies of variants in several neuropeptide genes in African and non-African populations. The results highlights SNPs in these genes that may also contribute to population disparities in prevalence of diseases such as hypertension and diabetes.

show abstract

“…Moreover, carboxypeptidase E, a prohormone sorting receptor, also interacts with lipid rafts via an amphipathic α helix . Recently, CgB has been shown to be able to penetrate inside biological membranes through its helicoidal domains to form an anion channel . Concerning CgA, several studies showed that the deletion of its N‐ or C‐terminal domains altered its secretion in distinct neuroendocrine cell lines .…”

Section: Chromogranin a Interacts With The Tgn Membrane To Direct Hormentioning

confidence: 99%

“…54 Recently, CgB has been shown to be able to penetrate inside biological membranes through its helicoidal domains to form an anion channel. 55 Concerning CgA, several studies showed that the deletion of its N-or Cterminal domains altered its secretion in distinct neuroendocrine cell lines. 10,35,50,56 Interestingly, the sequence identity between vertebrate CgA proteins is restricted to these terminal regions, 57 and expression of frog CgA in non-endocrine COS7 cells also resulted in the biogenesis of CgA-containing granules which release CgA and coexpressed hormones upon stimulation.…”

Section: Chromogranin a Interacts With The Tgn Membrane To Direct Hmentioning

confidence: 99%

“…In particular, Helle and colleagues showed that the CgA N-terminal peptide, vasostatin-I (VS-I, hCgA ), interacts with a membrane model in an amphiphilic penetration manner. 58 VS-I and hCgA [47][48][49][50][51][52][53][54][55][56][57][58][59][60][61][62][63][64][65][66] may also engage in hydrophobic interaction with membrane phospholipids at physiological conditions, VS-I enhancing the fluidity of saturated species of phosphatidylserine. 59,60 Another CgA-derived peptide named catestatin (hCgA 352-372 ) elicits histamine release from rat mast cells via its cationic and amphipathic properties.…”

Section: Chromogranin a Interacts With The Tgn Membrane To Direct Hmentioning

confidence: 99%

See 1 more Smart Citation

Chromogranin A in the early steps of the neurosecretory pathway

2019

View full text Add to dashboard Cite

Chromogranin A (CgA) is a soluble glycoprotein stored with hormones and neuropeptides in secretory granules (SG) of most (neuro)endocrine cells and neurons. Since its discovery in 1967, many studies have reported its structural characteristics, biological roles, and mechanisms of action. Indeed, CgA is both a precursor of various biologically active peptides and a granulogenic protein regulating the storage and secretion of hormones and neuropeptides. This review emphasizes the findings and theoretical concepts around the CgA‐linked molecular machinery controlling hormone/neuropeptide aggregation and the interaction of CgA‐hormone/neuropeptide aggregates with the trans‐Golgi membrane to allow hormone/neuropeptide targeting and SG biogenesis. We will also discuss the intriguing alteration of CgA expression and secretion in various neurological disorders, which could provide insights to elucidate the molecular mechanisms underlying these pathophysiological conditions.

show abstract

Secretory granule protein chromogranin B (CHGB) forms an anion channel in membranes

Cited by 12 publications

References 60 publications

Catalysis-dependent inactivation of human telomerase and its reactivation by intracellular telomerase-activating factors (iTAFs)

Catalysis-dependent inactivation of human telomerase and its reactivation by intracellular telomerase-activating factors (iTAFs)

Selected neuropeptide genes show genetic differentiation between Africans and non-Africans

Chromogranin A in the early steps of the neurosecretory pathway

Contact Info

Product

Resources

About