2014
DOI: 10.1016/j.devcel.2014.03.021
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A Two-Tier Golgi-Based Control of Organelle Size Underpins the Functional Plasticity of Endothelial Cells

Abstract: SummaryWeibel-Palade bodies (WPBs), endothelial-specific secretory granules that are central to primary hemostasis and inflammation, occur in dimensions ranging between 0.5 and 5 μm. How their size is determined and whether it has a functional relevance are at present unknown. Here, we provide evidence for a dual role of the Golgi apparatus in controlling the size of these secretory carriers. At the ministack level, cisternae constrain the size of nanostructures (“quanta”) of von Willebrand factor (vWF), the m… Show more

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Cited by 93 publications
(202 citation statements)
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“…Critically, this was not caused by Golgi fragmentation in siAP-1M1-treated cells, 27,28 (supplemental Figure 2) because we know this would affect WPB biogenesis. 29 Using BFA, we can also now show that most of this increase in unstimulated VWF release in siAP-1M1-treated cells is caused by an increase in secretion via the constitutive pathway, because a larger proportion was blocked with BFA ( Figure 4C). These results confirm that AP-1 is necessary for the sorting of VWF into WPB, and suggest that if this is disrupted, then the displaced VWF is continuously secreted through the constitutive pathway.…”
Section: Ap-1 and Vwf Polar Targetingmentioning
confidence: 96%
“…Critically, this was not caused by Golgi fragmentation in siAP-1M1-treated cells, 27,28 (supplemental Figure 2) because we know this would affect WPB biogenesis. 29 Using BFA, we can also now show that most of this increase in unstimulated VWF release in siAP-1M1-treated cells is caused by an increase in secretion via the constitutive pathway, because a larger proportion was blocked with BFA ( Figure 4C). These results confirm that AP-1 is necessary for the sorting of VWF into WPB, and suggest that if this is disrupted, then the displaced VWF is continuously secreted through the constitutive pathway.…”
Section: Ap-1 and Vwf Polar Targetingmentioning
confidence: 96%
“…First, we analyzed conditions for a single cisterna formation. A cisterna of Golgi ministacks represents a thin discoid structure with rumen thickness ∼20 nm (22), regulated rim thickness ∼50 nm (24), and variable width up to about 500 nm (28). There are two remarks from the energetic viewpoint.…”
Section: Modelmentioning
confidence: 99%
“…Because of the complex Golgi morphology and size variation of functionally distinct subcompartments, Golgi size control is likely more complex and must take into account altered transcriptional profiles of secretory cargo, the resident abundance of Golgi complex components, and direct signaling from the Golgi membrane surface (as reviewed in Sengupta and Linstedt 2011). Only recently it was shown that Golgi size and topology influence the size of its products, thereby establishing a direct link between organelle size and function (Ferraro et al 2014). Other potential examples of demand sensing include mitochondrial networks (Rafelski et al 2012), vacuole size scaling in yeast (Chan and Marshall 2014), and peroxisomes in the fungus Neurospora (Liu et al 2011).…”
Section: Intracellular Scaling Mechanismsmentioning
confidence: 99%