Chromogranin B (secretogranin I) promotes sorting to the regulated secretory pathway of processing intermediates derived from a peptide hormone precursor.

Natori, Shoichi; Huttner, Wieland B.

doi:10.1073/pnas.93.9.4431

Cited by 117 publications

(88 citation statements)

References 42 publications

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“…In CgA-deficient and POMC-expressing PC12 cells, POMC is secreted constitutively without secretory stimulation (45). Although POMC binds to CPE for its sorting to SGs (10), CgA is also essential for POMC sorting because it appears to co-aggregate POMC and its intermediates to SGs (39). As for CgA sorting to SGs, we propose the following hypothesis.…”

Section: Discussionmentioning

confidence: 99%

Secretogranin III Binds to Cholesterol in the Secretory Granule Membrane as an Adapter for Chromogranin A

Hosaka

Suda

Sakai

et al. 2004

Journal of Biological Chemistry

102

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Granin-family proteins, including chromogranin A (CgA) and secretogranin III (SgIII), are transported to secretory granules (SGs) in neuroendocrine cells. We previously showed that SgIII binds strongly to CgA in an intragranular milieu and targets CgA to SGs in pituitary and pancreatic endocrine cells. In this study, we demonstrated that with a sucrose density gradient of rat insulinoma-derived INS-1 cell homogenates, SgIII was localized to the SG fraction and was fractionated to the SG membrane (SGM) despite lacking the transmembrane region. With depletion of cholesterol from the SGM using methyl-␤-cyclodextrin, SgIII was impaired to bind to the SGM. Both SgIII and CgA were solubilized from the SGM by Triton X-100 in contrast to the Triton X-100 insolubility of carboxypeptidase E. SgIII and carboxypeptidase E strongly bound to the SGM-type liposome in intragranular conditions, but CgA did not. Instead, CgA bound to the SGM-type liposome only in the presence of SgIII. Immunocytochemical and pulse-chase experiments revealed that SgIII deleting the N-terminal lipid-binding region missorted to the constitutive pathway in mouse corticotroph-derived AtT-20 cells. Thus, we suggest that SgIII directly binds to cholesterol components of the SGM and targets CgA to SGs in pituitary and pancreatic endocrine cells.

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Section: Discussionmentioning

confidence: 99%

Secretogranin III Binds to Cholesterol in the Secretory Granule Membrane as an Adapter for Chromogranin A

Hosaka

Suda

Sakai

et al. 2004

Journal of Biological Chemistry

102

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“…Pancreatic beta cells and beta cell lines are also known to synthesise, in addition to insulin, a number of other secretory proteins, including members of the granin family, chromogranin A and chromogranin B (CgB) [7][8][9][10]. Based on intracellular distribution studies [7,8] and on data obtained in other cell lines (AtT20 and PC12), these granins are believed to play important roles both in the sorting, packaging and processing of secretion products [11][12][13][14], and in the storage of Ca 2+ within SG lumina [15]. Moreover chromogranin A and/or peptides derived from its processing have been reported to play autocrine, paracrine and endocrine functions upon discharge [16][17][18][19], while CgB has been shown to induce an autocrine inhibition of insulin release from beta cells [20].…”

Section: Introductionmentioning

confidence: 99%

Beta cell chromogranin B is partially segregated in distinct granules and can be released separately from insulin in response to stimulation

et al. 2008

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Aims/hypothesis We investigated, in three beta cell lines (INS-1E, RIN-5AH, betaTC3) and in human and rodent primary beta cells, the storage and release of chromogranin B, a secretory protein expressed in beta cells and postulated to play an autocrine role. We asked whether chromogranin B is stored together with and discharged in constant ratio to insulin upon various stimuli. Methods The intracellular distribution of insulin and chromogranin B was revealed by immunofluorescence followed by three-dimensional image reconstruction and by immunoelectron microscopy; their stimulated discharge was measured by ELISA and immunoblot analysis of homogenates and incubation media. Results Insulin and chromogranin B, co-localised in the Golgi complex/trans-Golgi network, appeared largely segregated from each other in the secretory granule compartment. In INS-1E cells, the percentage of granules positive only for insulin or chromogranin B and of those positive for both was 66, 7 and 27%, respectively. In resting cells, both insulin and chromogranin B were concentrated in the granule cores; upon stimulation, chromogranin B (but not insulin) was largely redistributed to the core periphery and the surrounding halo. Strong stimulation with a secretagogue mixture induced parallel release of insulin and chromogranin B, whereas with 3-isobutyl-1-methylxantine and forskolin ± high glucose release of chromogranin B predominated. Weak, Ca 2+ -dependent stimulation with ionomycin or carbachol induced exclusive release of chromogranin B, suggesting a higher Ca 2+ sensitivity of the specific granules. Conclusions/interpretation The unexpected complexity of the beta cell granule population in terms

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“…Lack of regulation of SgII and CgA transcription rate over the oestrous cycle in sheep revealed a further species difference. Also, changes in CgB mRNA levels may emphasise a role of CgB in regulating gonadotrophin secretion in sheep, particularly as CgB is involved in sorting of regulated proteins (Chanat et al 1993, 1994, Natori & Huttner 1996, Natori et al 1998.…”

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confidence: 99%

Co-localisation of gonadotrophins and granins in gonadotrophs at different stages of the oestrous cycle in sheep

Crawford

McNeilly²

2002

Journal of Endocrinology

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Associations between granins (secretogranin II (SgII) and chromogranin A and B (CgA and CgB)) and gonadotrophins (LH and FSH) have been reported in rodents and they may interact to facilitate differential storage and secretion of LH and FSH. This study investigated the relationship between granins and gonadotrophins in sheep at different stages of the oestrous cycle. Thirty-four cycling ewes had their oestrous cycles synchronised, and were divided into late luteal (LL; n=5) and early (EF; n=4), mid (n=3) and late (LF; n=11) follicular stages, and 24-53 h (n=5), 80-100 h (n=3) and 120-144 h (n=3) after the preovulatory LH surge (PS). LH mRNA levels were low in LF ewes (when plasma levels and pulse frequency of LH were high) but had increased by 80-100 h PS. In contrast, FSH mRNA levels decreased during the follicular phase and plasma FSH concentrations followed a similar pattern, to peak at 24-53 h PS due to low plasma oestradiol levels. While -gonadotrophin subunit ( -GSU), SgII and CgA mRNA levels did not change, CgB mRNA levels were elevated in EF ewes and had declined in ewes around the surge. Four distinctly sized mRNA transcripts (1·3, 2·0, 2·8 and 3·2 kb) were observed for CgA mRNA, while a double band was observed for LH mRNA that was subsequently reduced to a single band after 3 -poly(A) tail truncation. The long and short LH transcripts were prevalent in follicular and luteal ewes respectively. Numbers of LH +ve /FSH -ve granules stored within gonadotrophs were not different in LL and LF ewes (even though proportions of LH +ve granules were higher in LF ewes), but were reduced at 24-53 h PS. The majority of LH +ve granules also contained SgII, although few CgA +ve granules were found. Granule partitioning was evident whereby FSH and CgA were located near the periphery, and LH and SgII throughout the matrix. In conclusion, increases in both storage of LH +ve granules and secretion of LH in LF ewes despite constant LH mRNA levels was facilitated, at least in part, by improved LH mRNA transcript stability. Fewer LH +ve /FSH -ve granules were in storage after the PS, which was mirrored by a reduction in LH pulsatile release. Surprisingly, in view of results in rodents indicating significant changes, SgII and CgA mRNA levels did not change over the oestrous cycle in sheep. Conversely, CgB mRNA levels decreased around the time of PS. These novel results illustrate major differences in granin-gonadotrophin interactions between sheep and rodents.

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Chromogranin B (secretogranin I) promotes sorting to the regulated secretory pathway of processing intermediates derived from a peptide hormone precursor.

Cited by 117 publications

References 42 publications

Secretogranin III Binds to Cholesterol in the Secretory Granule Membrane as an Adapter for Chromogranin A

Secretogranin III Binds to Cholesterol in the Secretory Granule Membrane as an Adapter for Chromogranin A

Beta cell chromogranin B is partially segregated in distinct granules and can be released separately from insulin in response to stimulation

Co-localisation of gonadotrophins and granins in gonadotrophs at different stages of the oestrous cycle in sheep

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