Biogenesis of Dense-Core Secretory Granules

Bowman, Grant R.; Cowan, Andrew T.; Turkewitz, Aaron P.

doi:10.1007/978-0-387-93877-6_10

Cited by 5 publications

(3 citation statements)

References 184 publications

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“…LRRK2 recruits Rab2a onto DCVs for lysozyme sorting DCV cargo sorting begins in the trans-Golgi network and persists throughout DCV maturation, during which factors not destined for DCVs are directed to the endosomal-lysosomal route 28,29 .…”

Section: Lysozyme In Lrrk2 −/− Paneth Cells Is Degraded In Lysosomesmentioning

confidence: 99%

Commensal bacteria direct selective cargo sorting to promote symbiosis

et al. 2015

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Mucosal immunity protects a host from intestinal inflammation and infection and is profoundly influenced by symbiotic bacteria. Here we report that in mice symbiotic bacteria directed selective cargo sorting in Paneth cells to promote symbiosis through Nod2, a cytosolic bacterial sensor, and the multifunctional protein kinase LRRK2, both encoded by inflammatory bowel disease (IBD)-associated genes. Commensals recruited Nod2 onto lysozyme-containing dense core vesicles (DCVs), which was required for DCV localization of LRRK2 and a small GTPase, Rab2a. Deficiency of Nod2, LRRK2 or Rab2a or depletion of commensals resulted in lysosomal degradation of lysozyme. Thus, commensal bacteria and host factors orchestrate the lysozyme-sorting process to protect the host from enteric infection, implicating Paneth cell dysfunction in IBD pathogenesis.

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Section: Lysozyme In Lrrk2 −/− Paneth Cells Is Degraded In Lysosomesmentioning

confidence: 99%

Commensal bacteria direct selective cargo sorting to promote symbiosis

et al. 2015

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“…A) (Tokuyasu and Scherbaum, ; Bannister, ; Michael et al, ). In both animals and Ciliates, the cores are formed by protein assembly that is controlled by proteolytic processing (Adoutte et al, ; Turkewitz et al, ; Steiner et al, ) Moreover, the core proteins in Ciliates and animals are similar in their acidity (Chilcoat et al, ), their capacity for low‐affinity calcium binding (Turkewitz et al, ; Verbsky and Turkewitz, ) and their tendency to aggregate (Gorr et al, ; Chanat and Huttner, ) within the secretory pathway (Rambourg et al, ; Rahaman et al, ) The last of these properties is likely to be a key mechanism involved in protein sorting to dense core granules and mucocysts/trichocysts, respectively (Arvan and Castle, ; Jain et al, ; Bowman et al, ). Notwithstanding these and other similarities, there is no evidence that dense core granules and mucocysts/trichocysts arose from the same ancestral organelle (Elde et al, ).…”

Section: Independent Origins Of Regulated Peptide Secretion?mentioning

confidence: 99%

Tetrahymena thermophila: A divergent perspective on membrane traffic

Briguglio

Turkewitz

2014

J Exp Zool Pt B

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Tetrahymena thermophila, a member of the Ciliates, represents a class of organisms distantly related from commonly used model organisms in cell biology, and thus offers an opportunity to explore potentially novel mechanisms and their evolution. Ciliates, like all eukaryotes, possess a complex network of organelles that facilitate both macromolecular uptake and secretion. The underlying endocytic and exocytic pathways are key mediators of a cell’s interaction with its environment, and may therefore show niche-specific adaptations. Our laboratory has taken a variety of approaches to identify key molecular determinants for membrane trafficking pathways in Tetrahymena. Studies of Rab GTPases, dynamins, and sortilin-family receptors substantiate the widespread conservation of some features but also uncover surprising roles for lineage-restricted innovation.

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“…Protein and peptide hormones enter the secretory pathway while they are being synthesized by ribosomes on the endoplasmic reticulum and sorted into DCVs at the trans-Golgi network (TGN) (Borgonovo et al , 2006; Bowman et al , 2009). Small molecules, such as serotonin, are directly taken up by vesicular monoamine transporters (VMATs) from the cytoplasm to the lumen of DCVs (Sudhof, 2004).…”

Section: Introductionmentioning

confidence: 99%

High Throughput NPY-Venus and Serotonin Secretion Assays for Regulated Exocytosis in Neuroendocrine Cells

Zhang

Martin

2018

BIO-PROTOCOL

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Here we describe two assays to measure dense core vesicle (DCV) exocytosis-mediated cargo secretion in neuroendocrine cells. To conduct siRNA screens for novel genes in regulated DCV exocytosis, we developed a plate reader-based secretion assay using DCV cargo, NPY-Venus, and an orthogonal 3H-serotonin secretion assay. The NPY-Venus secretion assay was successfully used for a high throughput siRNA screen, and the serotonin secretion assay was used to validate hits identified from the screen (Sorensen, 2017; Zhang et al., 2017).

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Biogenesis of Dense-Core Secretory Granules

Cited by 5 publications

References 184 publications

Commensal bacteria direct selective cargo sorting to promote symbiosis

Commensal bacteria direct selective cargo sorting to promote symbiosis

Tetrahymena thermophila: A divergent perspective on membrane traffic

High Throughput NPY-Venus and Serotonin Secretion Assays for Regulated Exocytosis in Neuroendocrine Cells

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