Dense-Core Secretory Granule Biogenesis

Kim, Taeyoon; Gondré–Lewis, Marjorie C.; Arnaoutova, Irina; Loh, Y. Peng

doi:10.1152/physiol.00043.2005

Cited by 172 publications

(212 citation statements)

References 91 publications

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“…Secreted proteins that enter regulated pathway exit the transGolgi network into DCGs (15). First, we assessed the colocalization of FSHβ with chromogranin-A (Chr-A) (Fig.…”

Section: Significancementioning

confidence: 99%

Redirecting intracellular trafficking and the secretion pattern of FSH dramatically enhances ovarian function in mice

Wang¹,

Larson²,

Jablonka‐Shariff

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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FSH and luteinizing hormone (LH) are secreted constitutively or in pulses, respectively, from pituitary gonadotropes in many vertebrates, and regulate ovarian function. The molecular basis for this evolutionarily conserved gonadotropin-specific secretion pattern is not understood. Here, we show that the carboxyterminal heptapeptide in LH is a gonadotropin-sorting determinant in vivo that directs pulsatile secretion. FSH containing this heptapeptide enters the regulated pathway in gonadotropes of transgenic mice, and is released in response to gonadotropin-releasing hormone, similar to LH. FSH released from the LH secretory pathway rescued ovarian defects in Fshb-null mice as efficiently as constitutively secreted FSH. Interestingly, the rerouted FSH enhanced ovarian follicle survival, caused a dramatic increase in number of ovulations, and prolonged female reproductive lifespan. Furthermore, the rerouted FSH vastly improved the in vivo fertilization competency of eggs, their subsequent development in vitro and when transplanted, the ability to produce offspring. Our study demonstrates the feasibility to fine-tune the target tissue responses by modifying the intracellular trafficking and secretory fate of a pituitary trophic hormone. The approach to interconvert the secretory fate of proteins in vivo has pathophysiological significance, and could explain the etiology of several hormone hyperstimulation and resistance syndromes.protein sorting | regulated secretion | dense core granules | folliculogenesis

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“…Secreted proteins that enter regulated pathway exit the transGolgi network into DCGs (15). First, we assessed the colocalization of FSHβ with chromogranin-A (Chr-A) (Fig.…”

Section: Significancementioning

confidence: 99%

Redirecting intracellular trafficking and the secretion pattern of FSH dramatically enhances ovarian function in mice

Wang¹,

Larson²,

Jablonka‐Shariff

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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“…Neurons and endocrine cells, such as chromaffin cells in adrenal glands and β-cells in pancreatic islets, employ DCV-mediated exocytosis to release a wide range of cargos in response to different physiological conditions. Two complementary mechanisms have been proposed for DCV cargo sorting: (i) sorting by entry, and (ii) sorting by retention (Kim et al, 2006). Physical aggregation of cargos, either alone or together with chromogranins, is important for their sorting and retention within DCVs (Kim et al, 2006).…”

Section: The Cellular Processes Modulated By Commensal Bacteria In Pamentioning

confidence: 99%

“…Two complementary mechanisms have been proposed for DCV cargo sorting: (i) sorting by entry, and (ii) sorting by retention (Kim et al, 2006). Physical aggregation of cargos, either alone or together with chromogranins, is important for their sorting and retention within DCVs (Kim et al, 2006). However, apart from physical aggregation, little is understood about how DCV cargos are retained within DCVs while factors not destined for DCVs are directed to the endosomal/lysosomal route during DCV maturation.…”

Section: The Cellular Processes Modulated By Commensal Bacteria In Pamentioning

confidence: 99%

Paneth cells: the hub for sensing and regulating intestinal flora

Zhang

Liu

2016

Sci. China Life Sci.

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The complex interplay between symbiotic bacteria and host immunity plays a key role in shaping intestinal homeostasis and maintaining host health. Paneth cells, as one of the major producers of antimicrobial peptides in the intestine under steady-state conditions, play a vital role in regulating intestinal flora. Many studies on inflammatory bowel disease (IBD)-associated genes have put Paneth cells at the center of IBD pathogenesis. In this perspective, we focus on mechanistic studies of different cellular processes in Paneth cells that are regulated by various IBD-associated susceptibility genes, and we discuss the hypothesis that Paneth cells function as the central hub for sensing and regulating intestinal flora in the maintenance of intestinal homeostasis. inflammatory bowel disease, Paneth cell, commensal bacteria, intestinal homeostasisCitation:

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“…Researchers are working on defining molecular interactions that affect sorting pathways in exocrine cells; however all the known mechanisms are not present in other cell types. In neuroendocrine and endocrine cells the pH of the secretory granules decrease during maturation from 6.2 at the trans Golgi network (TGN) to 5.5-5.0 in the mature granule [22][23][24]. This acidic environment is important for correct sorting and protein aggregation of certain cells [24].…”

Section: Mechanism Of Parotid Gland Secretionmentioning

confidence: 99%

“…In neuroendocrine and endocrine cells the pH of the secretory granules decrease during maturation from 6.2 at the trans Golgi network (TGN) to 5.5-5.0 in the mature granule [22][23][24]. This acidic environment is important for correct sorting and protein aggregation of certain cells [24]. In the parotid gland, the pH of the acinar cell granule increases from about pH 6.2 at the TGN to 6.8 or higher after maturation [25].…”

Section: Mechanism Of Parotid Gland Secretionmentioning

confidence: 99%

The dimerization of parotid secretory protein.

Blau¹

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Dense-Core Secretory Granule Biogenesis

Cited by 172 publications

References 91 publications

Redirecting intracellular trafficking and the secretion pattern of FSH dramatically enhances ovarian function in mice

Redirecting intracellular trafficking and the secretion pattern of FSH dramatically enhances ovarian function in mice

Paneth cells: the hub for sensing and regulating intestinal flora

The dimerization of parotid secretory protein.

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