VAMP8/Endobrevin is a critical factor for the homotypic granule growth in pancreatic acinar cells

Hammel, Ilan; Wang, Cheng-Chun; Hong, Wanjin; Amihai, Dina

doi:10.1007/s00441-012-1400-1

Cited by 7 publications

(6 citation statements)

References 51 publications

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“…In particular, interactions with the endocytic system might be amplified in cells expressing the CA Rab5A mutant. It is also interesting to note that VAMP8 has recently been implicated as playing a role in homotypic SG fusion during genesis (69) and compound exocytosis in pancreatic acinar cells (70). We observed an enhanced rate of exocytosis in CA Rab5A-expressing cells.…”

Section: Discussionsupporting

confidence: 61%

Rab5 Is a Novel Regulator of Mast Cell Secretory Granules: Impact on Size, Cargo, and Exocytosis

Azouz

Zur

Efergan

et al. 2014

The Journal of Immunology

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Secretion of inflammatory mediators prestored in mast cells secretory granules (SGs) enhances immune responses such as in allergy and host defense. However, the mechanisms underlying the biogenesis of the SGs remain largely unresolved. By combining high-resolution live cell imaging and quantitative morphometric analyses, we show that the small GTPase Rab5 controls the SG size and cargo composition by a VAMP8-dependent fusion mechanism. Knockdown of the endogenous Rab5, or expression of constitutively negative mutants, significantly reduces the size of SGs and increases their number. Conversely, expression of constitutively active Rab5 mutants induces few, but giant, SGs. Both the small and giant SGs maintain their exocytosis competence. Finally, we show that Rab5-mediated fusion between Golgi-derived SGs and early endosomes precedes the maturation of the SGs, as reflected by the recruitment of Rab27B, and allows the incorporation of cargo, such as CD63, that traffics through endosomes. Collectively, our results assign Rab5 a key role in mediating mast cell SG fusion during biogenesis, thereby controlling the amount and composition of the SGs content and maintaining the communication between new and pre-existing SGs.

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Section: Discussionsupporting

confidence: 61%

Rab5 Is a Novel Regulator of Mast Cell Secretory Granules: Impact on Size, Cargo, and Exocytosis

Azouz

Zur

Efergan

et al. 2014

The Journal of Immunology

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“…The prevalence of sequential exocytosis may, therefore, be underestimated. Sequential exocytosis has been observed in exocrine acinar cells (224,443,444), adrenal chromaffin cells (7,190,321), PC12 cells (322,734), ␤ cells (464,632), pituitary lactotrophs (116), human neuroendocrine Bon cells (652), the nasal gland (469), eosinophils (218), and mast cells (8,213), and even in bipolar synapses (398). Sequential exocytosis is particularly prominent in exocrine acinar cells and chromaffin cells, as described below.…”

Section: Sequential Exocytosismentioning

confidence: 85%

“…Syntaxin may also be a diffusive factor, particularly when the fusion pore is widely open, as has been reported in exocrine cells (493). Exocrine acinar cells express syntaxin3 and VAMP8 for granule-granule fusion during sequential exocytosis (43, 224), and the unitary-SNARE configuration may be utilized during multigranular exocytosis. In neutrophils, SNAP23 is expressed in secretory vesicles (592), perhaps providing a reason for the abundance of multigranular exocytosis (218), in which vesicle-vesicle fusion precedes exocytosis.…”

Section: Possible Examples Of Unitary Configurations In Endocrine Celmentioning

confidence: 92%

Distinct Initial SNARE Configurations Underlying the Diversity of Exocytosis

Kasai

Takahashi

Tokumaru

2012

Physiological Reviews

143

124

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The dynamics of exocytosis are diverse and have been optimized for the functions of synapses and a wide variety of cell types. For example, the kinetics of exocytosis varies by more than five orders of magnitude between ultrafast exocytosis in synaptic vesicles and slow exocytosis in large dense-core vesicles. However, in all cases, exocytosis is mediated by the same fundamental mechanism, i.e., the assembly of soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins. It is often assumed that vesicles need to be docked at the plasma membrane and SNARE proteins must be preassembled before exocytosis is triggered. However, this model cannot account for the dynamics of exocytosis recently reported in synapses and other cells. For example, vesicles undergo exocytosis without prestimulus docking during tonic exocytosis of synaptic vesicles in the active zone. In addition, epithelial and hematopoietic cells utilize cAMP and kinases to trigger slow exocytosis of nondocked vesicles. In this review, we summarize the manner in which the diversity of exocytosis reflects the initial configurations of SNARE assembly, including trans-SNARE, binary-SNARE, unitary-SNARE, and cis-SNARE configurations. The initial SNARE configurations depend on the particular SNARE subtype (syntaxin, SNAP25, or VAMP), priming proteins (Munc18, Munc13, CAPS, complexin, or snapin), triggering proteins (synaptotagmins, Doc2, and various protein kinases), and the submembraneous cytomatrix, and they are the key to determining the kinetics of subsequent exocytosis. These distinct initial configurations will help us clarify the common SNARE assembly processes underlying exocytosis and membrane trafficking in eukaryotic cells.

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“…The protein is required for granule secretion [21,22]. VAMP8 forms core SNARE complexes with different partners in different tissues or cell lines [23]. In PC12 cells and NRK cells VAMP8 interacts with syntaxin 7 and 8, as well as Vtilb [24,25].…”

Section: Discussionmentioning

confidence: 99%

“…In pancreatic acinar cell granule membranes, VAMP8 interacts with syntaxins 2 and 3 as well as SNAP-23 [23]. VAMP8 participates in the formation and is required for fusion of pancreatic acinar cell granules [23,28], which are significantly smaller in VAMP8 knockout mice than in wild type mice [23]. …”

Section: Discussionmentioning

confidence: 99%

Chorein Sensitive Dopamine Release from Pheochromocytoma (PC12) Cells

Honisch¹,

Fehrenbacher

Lebedeva

et al. 2015

Neurosignals

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Background: Chorein, a protein supporting activation of phosphoinositide 3 kinase (PI3K), participates in the regulation of actin polymerization and cell survival. A loss of function mutation of the chorein encoding gene VPS13A (vacuolar protein sorting-associated protein 13A) leads to chorea-acanthocytosis (ChAc), a neurodegenerative disorder with simultaneous erythrocyte akanthocytosis. In blood platelets chorein deficiency has been shown to compromise expression of vesicle-associated membrane protein 8 (VAMP8) and thus degranulation. The present study explored whether chorein is similarly involved in VAMP8 expression and dopamine release of pheochromocytoma (PC12) cells. Methods: Chorein was down-regulated by silencing in PC12 cells. Transmission electron microscopy was employed to quantify the number of vesicles, RT-PCR to determine transcript levels, Western blotting to quantify protein expression and ELISA to determine dopamine release. Results: Chorein silencing significantly reduced the number of vesicles, VAMP8 transcript levels and VAMP8 protein abundance. Increase of extracellular K⁺ from 5 mM to 40 mM resulted in marked stimulation of dopamine release, an effect significantly blunted by chorein silencing. Conclusions: Chorein deficiency down-regulates VAMP8 expression, vesicle numbers and dopamine release in pheochromocytoma cells.

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VAMP8/Endobrevin is a critical factor for the homotypic granule growth in pancreatic acinar cells

Cited by 7 publications

References 51 publications

Rab5 Is a Novel Regulator of Mast Cell Secretory Granules: Impact on Size, Cargo, and Exocytosis

Rab5 Is a Novel Regulator of Mast Cell Secretory Granules: Impact on Size, Cargo, and Exocytosis

Distinct Initial SNARE Configurations Underlying the Diversity of Exocytosis

Chorein Sensitive Dopamine Release from Pheochromocytoma (PC12) Cells

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