Differential sorting behavior for soluble and transmembrane cargoes at the <i>trans</i>-Golgi network in endocrine cells

Hummer, Blake H.; Maslar, Drew; Soltero-Gutierrez, Margarita; Leeuw, Noah F. de; Asensio, Cédric S.

doi:10.1091/mbc.e19-10-0561

Cited by 17 publications

(14 citation statements)

References 40 publications

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“…The distribution of distances is similar for Syt-1 and Syt-7, and increased upon randomization (inversion of the CgAstack), consistent with the notion that most CgA-vesicles harbor both Syt-1 and Syt-7. The distance is consistent with the Syts being anchored in the vesicle, although other possibilities remain; for instance Syts might be present in small transport vesicles, to be delivered to the CgA-vesicle shortly before fusion (Hummer et al, 2020;Walter et al, 2014). However, in that case a large number of small vesicles should surround the dense-core vesicles, which we find no evidence for in high-resolution EM (Fig.…”

Section: Functional Interactions Between Synaptotagminssupporting

confidence: 74%

Synaptotagmin-7 places dense-core vesicles at the cell membrane to promote Munc13-2- and Ca2+-dependent priming

Tawfik

Martins

Houy

et al. 2021

eLife

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Synaptotagmins confer calcium-dependence to the exocytosis of secretory vesicles, but how coexpressed synaptotagmins interact remains unclear. We find that synaptotagmin-1 and synaptotagmin-7 when present alone act as standalone fast and slow Ca2+-sensors for vesicle fusion in mouse chromaffin cells. When present together, synaptotagmin-1 and synaptotagmin-7 are found in largely non-overlapping clusters on dense-core vesicles. Synaptotagmin-7 stimulates Ca2+-dependent vesicle priming and inhibits depriming, and it promotes ubMunc13-2- and phorbolester-dependent priming, especially at low resting calcium concentrations. The priming effect of synaptotagmin-7 increases the number of vesicles fusing via synaptotagmin-1, while negatively affecting their fusion speed, indicating both synergistic and competitive interactions between synaptotagmins. Synaptotagmin-7 places vesicles in close membrane apposition (<6 nm); without it, vesicles accumulate out of reach of the fusion complex (20-40 nm). We suggest that a synaptotagmin-7-dependent movement toward the membrane is involved in Munc13-2/phorbolester/Ca2+-dependent priming as a prelude to fast and slow exocytosis triggering.

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Section: Functional Interactions Between Synaptotagminssupporting

confidence: 74%

Synaptotagmin-7 places dense-core vesicles at the cell membrane to promote Munc13-2- and Ca2+-dependent priming

Tawfik

Martins

Houy

et al. 2021

eLife

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“…STR-Linker-KDEL was used as the endoplasmic reticulum (ER) hook. Neuropeptide Y (NPY)-EGFP-streptavidin binding protein (SBP), NPY-pHluorin-SBP, phogrin-GFP-SBP, and VMAT2-GFP-SBP were generated and used as cargo plasmids ( 23 ).…”

Section: Methodsmentioning

confidence: 99%

“…Images were binned (two by two), and cells were excited by 340 nm and 380 nm light every 500 ms with a 100-ms interval between exposures. Cells were imaged for 45 s under basal conditions prior to perfusing cells with a 90 mmol/L K+ KRB solution for 45 s. RUSH assays have been described before ( 23 ).…”

Section: Methodsmentioning

confidence: 99%

“…For this, we relied on the 'retention using selective hook' (RUSH) system (Boncompain et al, 2012), which allows to synchronize and visualize the movement of cargoes along the secretory pathway. This assay, that we recently optimized for endocrine cells (Hummer et al, 2020), uses localized expression of streptavidin within the endoplasmic reticulum (ER) as a hook to trap a co-expressed secretory cargo fused to streptavidin-binding peptide. Addition of biotin leads to the release of a discrete, synchronized wave of the secretory cargo, in this case, NPY-GFP-SBP, a soluble marker of SGs.…”

Section: Vps41 Ko Cells Display Normal Tgn Budding Kinetics But Transmembrane Protein Missortingmentioning

confidence: 99%

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Pancreatic β-Cell–Specific Deletion of VPS41 Causes Diabetes Due to Defects in Insulin Secretion

et al. 2020

Self Cite

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Insulin secretory granules (SGs) mediate the regulated secretion of insulin, which is essential for glucose homeostasis. The basic machinery responsible for this regulated exocytosis consists of specific proteins present both at the plasma membrane and on insulin SGs. The protein composition of insulin SGs thus dictates their release properties, yet the mechanisms controlling insulin SG formation, which determine this molecular composition, remain poorly understood. VPS41, a component of the endolysosomal tethering homotypic fusion and vacuole protein sorting (HOPS) complex, was recently identified as a cytosolic factor involved in the formation of neuroendocrine and neuronal granules. We now find that VPS41 is required for insulin SG biogenesis and regulated insulin secretion. Loss of VPS41 in pancreatic β-cells leads to a reduction in insulin SG number, changes in their transmembrane protein composition, and defects in granule-regulated exocytosis. Exploring a human point mutation, identified in patients with neurological but no endocrine defects, we show that the effect on SG formation is independent of HOPS complex formation. Finally, we report that mice with a deletion of VPS41 specifically in β-cells develop diabetes due to severe depletion of insulin SG content and a defect in insulin secretion. In sum, our data demonstrate that VPS41 contributes to glucose homeostasis and metabolism.

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“…e subcellular position of the Golgi apparatus is different from that of various eukaryotic cells. In most eukaryotic cells, the Golgi apparatus includes cis-Golgi and trans-Golgi [11,12]. Cis-Golgi is mainly composed of vesicles and multiple vesicles form the Golgi pile.…”

Section: Introductionmentioning

confidence: 99%

SubRF_Seq: Identification of Sub-Golgi Protein Types with Random Forest with Partial Sequence Information

Cui

Cao

Bao

et al. 2020

Scientific Programming

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In the recent years, the subject of Golgi classification has been studied intensively. It has been scientifically proven that Golgi can synthesize many substances, such as polysaccharides, and it can also combine proteins with sugars or lipids with glycoproteins and lipoproteins. In some cells (such as liver cells), the Golgi apparatus is also involved in the synthesis and secretion of lipoproteins. Therefore, the loss of Golgi protein function may have severe effects on the human body. For example, Alzheimer’s disease and diabetes are related to the loss of Golgi protein function. Because the classification of Golgi proteins has a specific effect on the treatment of these diseases, many scholars have studied the classification of Golgi proteins, but the data sets they used were complete Golgi sequences. The focus of this article is whether there is redundancy in the Golgi protein classification or, in other words, whether a part of the entire Golgi protein sequence can be used to complete the Golgi protein classification. Besides, we have adopted a new method to deal with the problem of sample imbalance. After experiments, our model has certain observability.

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Differential sorting behavior for soluble and transmembrane cargoes at the trans-Golgi network in endocrine cells

Cited by 17 publications

References 40 publications

Synaptotagmin-7 places dense-core vesicles at the cell membrane to promote Munc13-2- and Ca2+-dependent priming

Synaptotagmin-7 places dense-core vesicles at the cell membrane to promote Munc13-2- and Ca2+-dependent priming

Pancreatic β-Cell–Specific Deletion of VPS41 Causes Diabetes Due to Defects in Insulin Secretion

SubRF_Seq: Identification of Sub-Golgi Protein Types with Random Forest with Partial Sequence Information

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