Secretion induces cell pH dynamics impacting assembly-disassembly of the fusion protein complex: A combined fluorescence and atomic force microscopy study

Lewis, Kenneth T.; Naik, Akshata R.; Laha, Suvra S.; Wang, Sunxi; Mao, Guangzhao; Kuhn, Eric R.; Jena, Bhanu P.

doi:10.1016/j.semcdb.2017.08.003

“…Similar to synaptic vesicles where Go, potassium ion channel, vH + -ATPase and AQP6 are among the players involved in volume regulation required for neurotransmitter release, insulin vesicle swelling as a consequence of rapid water gating via AQP7 previously identified in beta cells 20 could be involved in glucose-stimulated insulin secretion. Furthermore, these results are in confirmation with recent studies 21 demonstrating that Valproate, the FDA approved antiepileptic drug perturbs insulin granule-associated vH + -ATPase by preventing the association of the vH + -. CC-BY-NC-ND 4.0 International license a certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.…”

Section: Exposure Of Min6 Cells To Bafilomycin a Reduces Insulin Granule Association With The Cell Plasma Membranesupporting

confidence: 88%

vH+-ATPase-induced intracellular acidification is critical to glucose-stimulated insulin secretion in beta cells

Naik

¹

,

Formosa

²

,

Pulvender

³

et al. 2020

Histochem Cell Biol

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Swelling of secretory vesicles is critical for the regulated expulsion of intravesicular contents from cells during secretion. At the secretory vesicle membrane of the exocrine pancreas and neurons, GTP-binding G proteins, vH + -ATPase, potassium channels and AQP water channels, are among the players implicated in vesicle volume regulation. Here we report in insulin secreting MIN6 cells, the requirement of vH + -ATPase-mediated intracellular acidification on glucosestimulated insulin release. MIN6 cells exposed to the vH + -ATPase inhibitor Bafilomycin A show decreased acidification of the cytosolic compartment that include insulin-carrying granules. Additionally, a loss of insulin granule association with the cell plasma membrane is demonstrated following Bafilomycin A treatment and results in a decrease in glucose-stimulated insulin secretion and accumulation of intracellular insulin. These results suggest that vH + -ATPase-mediated intracellular acidification is required both at the level of secretory vesicles and the cell plasma membrane for cell secretion.

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“…Furthermore, these results are in confirmation with recent studies 21 demonstrating that Valproate, the FDA approved antiepileptic drug perturbs insulin granule-associated vH + -ATPase by preventing the association of the vH + -ATPase subunit C to the complex, thereby inhibits glucose-stimulated insulin secretion from MIN6 cells. Similarly, the critical role of intracellular acidification on decreasing t-/v-SNARE complex disassembly by the soluble Nethylmaleimide-sensitive factor NSF, promoting fusion of secretory vesicles at the cell plasma membrane 22 , has also been demonstrated.…”

Section: Exposure Of Min6 Cells To Bafilomycin a Reduces Insulin Gransupporting

confidence: 88%

“…When vesicle acidification is prevented by cellular exposure to Bafilomycin A to inhibit vH + -ATPase, insulin release dropped significantly. Similar to synaptic vesicles where Go, potassium ion channel, vH + -ATPase and AQP6 are among the players involved in volume regulation required for neurotransmitter release, insulin vesicle swelling as a consequence of rapid water gating via AQP7 previously identified in beta cells 20 could be involved in glucose-stimulated insulin secretion.Furthermore, these results are in confirmation with recent studies21 demonstrating that Valproate, the FDA approved antiepileptic drug perturbs insulin granule-associated vH + -ATPase by preventing the association of the vH + -ATPase subunit C to the complex, thereby inhibits glucose-stimulated insulin secretion from MIN6 cells. Similarly, the critical role of intracellular acidification on decreasing t-/v-SNARE complex disassembly by the soluble Nethylmaleimide-sensitive factor NSF, promoting fusion of secretory vesicles at the cell plasma membrane22 , has also been demonstrated.…”

supporting

confidence: 88%

vH⁺-ATPase-induced intracellular acidification is critical to glucose-stimulated insulin secretion

Naik

¹

,

Formosa

²

,

Pulvender

³

et al. 2019

Preprint

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Swelling of secretory vesicles is critical for the regulated expulsion of intravesicular contents from cells during secretion. At the secretory vesicle membrane of the exocrine pancreas and neurons, GTP-binding G proteins, vH + -ATPase, potassium channels and AQP water channels, are among the players implicated in vesicle volume regulation. Here we report in insulin secreting MIN6 cells, the requirement of vH + -ATPase-mediated intracellular acidification on glucosestimulated insulin release. MIN6 cells exposed to the vH + -ATPase inhibitor Bafilomycin A show decreased acidification of the cytosolic compartment that include insulin-carrying granules. Additionally, a loss of insulin granule association with the cell plasma membrane is demonstrated following Bafilomycin A treatment and results in a decrease in glucose-stimulated insulin secretion and accumulation of intracellular insulin. These results suggest that vH + -ATPase-mediated intracellular acidification is required both at the level of secretory vesicles and the cell plasma membrane for cell secretion. Corresponding Author

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Effect of Toll-Like Receptor 4/Myeloid Differentiation Factor 88 Inhibition by Salvianolic Acid B on Neuropathic Pain After Spinal Cord Injury in Mice

Wang

¹

,

Xu

²

,

Hu

³

et al. 2019

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Secretion induces cell pH dynamics impacting assembly-disassembly of the fusion protein complex: A combined fluorescence and atomic force microscopy study

Cited by 3 publications

References 27 publications

vH+-ATPase-induced intracellular acidification is critical to glucose-stimulated insulin secretion in beta cells

vH+-ATPase-induced intracellular acidification is critical to glucose-stimulated insulin secretion in beta cells

vH⁺-ATPase-induced intracellular acidification is critical to glucose-stimulated insulin secretion

Effect of Toll-Like Receptor 4/Myeloid Differentiation Factor 88 Inhibition by Salvianolic Acid B on Neuropathic Pain After Spinal Cord Injury in Mice

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