V-ATPase modulates exocytosis in neuroendocrine cells through the activation of the ARNO-Arf6-PLD pathway and the synthesis of phosphatidic acid
Although there is mounting evidence indicating that lipids serve crucial functions in cells and are implicated in a growing number of human diseases, their precise roles remain largely unknown. This is particularly true in the case of neurosecretion, where fusion with the plasma membrane of specific...
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Frontiers Media S.A.
2023-04-01
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| Series: | Frontiers in Molecular Biosciences |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmolb.2023.1163545/full |
| _version_ | 1827971473903452160 |
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| author | Qili Wang Alexander Wolf Sebahat Ozkan Ludovic Richert Yves Mely Sylvette Chasserot-Golaz Stéphane Ory Stéphane Gasman Nicolas Vitale |
| author_facet | Qili Wang Alexander Wolf Sebahat Ozkan Ludovic Richert Yves Mely Sylvette Chasserot-Golaz Stéphane Ory Stéphane Gasman Nicolas Vitale |
| author_sort | Qili Wang |
| collection | DOAJ |
| description | Although there is mounting evidence indicating that lipids serve crucial functions in cells and are implicated in a growing number of human diseases, their precise roles remain largely unknown. This is particularly true in the case of neurosecretion, where fusion with the plasma membrane of specific membrane organelles is essential. Yet, little attention has been given to the role of lipids. Recent groundbreaking research has emphasized the critical role of lipid localization at exocytotic sites and validated the essentiality of fusogenic lipids, such as phospholipase D (PLD)-generated phosphatidic acid (PA), during membrane fusion. Nevertheless, the regulatory mechanisms synchronizing the synthesis of these key lipids and neurosecretion remain poorly understood. The vacuolar ATPase (V-ATPase) has been involved both in vesicle neurotransmitter loading and in vesicle fusion. Thus, it represents an ideal candidate to regulate the fusogenic status of secretory vesicles according to their replenishment state. Indeed, the cytosolic V1 and vesicular membrane-associated V0 subdomains of V-ATPase were shown to dissociate during the stimulation of neurosecretory cells. This allows the subunits of the vesicular V0 to interact with different proteins of the secretory machinery. Here, we show that V0a1 interacts with the Arf nucleotide-binding site opener (ARNO) and promotes the activation of the Arf6 GTPase during the exocytosis in neuroendocrine cells. When the interaction between V0a1 and ARNO was disrupted, it resulted in the inhibition of PLD activation, synthesis of phosphatidic acid during exocytosis, and changes in the timing of fusion events. These findings indicate that the separation of V1 from V0 could function as a signal to initiate the ARNO-Arf6-PLD1 pathway and facilitate the production of phosphatidic acid, which is essential for effective exocytosis in neuroendocrine cells. |
| first_indexed | 2024-04-09T19:09:31Z |
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| id | doaj.art-bd8a62949fee4ab58c8f7e73dd9ade3a |
| institution | Directory Open Access Journal |
| issn | 2296-889X |
| language | English |
| last_indexed | 2024-04-09T19:09:31Z |
| publishDate | 2023-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Biosciences |
| spelling | doaj.art-bd8a62949fee4ab58c8f7e73dd9ade3a2023-04-07T04:24:48ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2023-04-011010.3389/fmolb.2023.11635451163545V-ATPase modulates exocytosis in neuroendocrine cells through the activation of the ARNO-Arf6-PLD pathway and the synthesis of phosphatidic acidQili Wang0Alexander Wolf1Sebahat Ozkan2Ludovic Richert3Yves Mely4Sylvette Chasserot-Golaz5Stéphane Ory6Stéphane Gasman7Nicolas Vitale8Institut des Neurosciences Cellulaires et Intégratives, CNRS UPR 3212 and Université de Strasbourg, Strasbourg, FranceInstitut des Neurosciences Cellulaires et Intégratives, CNRS UPR 3212 and Université de Strasbourg, Strasbourg, FranceInstitut des Neurosciences Cellulaires et Intégratives, CNRS UPR 3212 and Université de Strasbourg, Strasbourg, FranceLaboratoire de Bioimagerie et Pathologies, Faculté de Pharmacie, CNRS UMR and Université de Strasbourg, Strasbourg, FranceLaboratoire de Bioimagerie et Pathologies, Faculté de Pharmacie, CNRS UMR and Université de Strasbourg, Strasbourg, FranceInstitut des Neurosciences Cellulaires et Intégratives, CNRS UPR 3212 and Université de Strasbourg, Strasbourg, FranceInstitut des Neurosciences Cellulaires et Intégratives, CNRS UPR 3212 and Université de Strasbourg, Strasbourg, FranceInstitut des Neurosciences Cellulaires et Intégratives, CNRS UPR 3212 and Université de Strasbourg, Strasbourg, FranceInstitut des Neurosciences Cellulaires et Intégratives, CNRS UPR 3212 and Université de Strasbourg, Strasbourg, FranceAlthough there is mounting evidence indicating that lipids serve crucial functions in cells and are implicated in a growing number of human diseases, their precise roles remain largely unknown. This is particularly true in the case of neurosecretion, where fusion with the plasma membrane of specific membrane organelles is essential. Yet, little attention has been given to the role of lipids. Recent groundbreaking research has emphasized the critical role of lipid localization at exocytotic sites and validated the essentiality of fusogenic lipids, such as phospholipase D (PLD)-generated phosphatidic acid (PA), during membrane fusion. Nevertheless, the regulatory mechanisms synchronizing the synthesis of these key lipids and neurosecretion remain poorly understood. The vacuolar ATPase (V-ATPase) has been involved both in vesicle neurotransmitter loading and in vesicle fusion. Thus, it represents an ideal candidate to regulate the fusogenic status of secretory vesicles according to their replenishment state. Indeed, the cytosolic V1 and vesicular membrane-associated V0 subdomains of V-ATPase were shown to dissociate during the stimulation of neurosecretory cells. This allows the subunits of the vesicular V0 to interact with different proteins of the secretory machinery. Here, we show that V0a1 interacts with the Arf nucleotide-binding site opener (ARNO) and promotes the activation of the Arf6 GTPase during the exocytosis in neuroendocrine cells. When the interaction between V0a1 and ARNO was disrupted, it resulted in the inhibition of PLD activation, synthesis of phosphatidic acid during exocytosis, and changes in the timing of fusion events. These findings indicate that the separation of V1 from V0 could function as a signal to initiate the ARNO-Arf6-PLD1 pathway and facilitate the production of phosphatidic acid, which is essential for effective exocytosis in neuroendocrine cells.https://www.frontiersin.org/articles/10.3389/fmolb.2023.1163545/fullchromaffin cellsV-ATPasephospholipase Dphospholipidsneurosecretionmembrane fusion |
| spellingShingle | Qili Wang Alexander Wolf Sebahat Ozkan Ludovic Richert Yves Mely Sylvette Chasserot-Golaz Stéphane Ory Stéphane Gasman Nicolas Vitale V-ATPase modulates exocytosis in neuroendocrine cells through the activation of the ARNO-Arf6-PLD pathway and the synthesis of phosphatidic acid Frontiers in Molecular Biosciences chromaffin cells V-ATPase phospholipase D phospholipids neurosecretion membrane fusion |
| title | V-ATPase modulates exocytosis in neuroendocrine cells through the activation of the ARNO-Arf6-PLD pathway and the synthesis of phosphatidic acid |
| title_full | V-ATPase modulates exocytosis in neuroendocrine cells through the activation of the ARNO-Arf6-PLD pathway and the synthesis of phosphatidic acid |
| title_fullStr | V-ATPase modulates exocytosis in neuroendocrine cells through the activation of the ARNO-Arf6-PLD pathway and the synthesis of phosphatidic acid |
| title_full_unstemmed | V-ATPase modulates exocytosis in neuroendocrine cells through the activation of the ARNO-Arf6-PLD pathway and the synthesis of phosphatidic acid |
| title_short | V-ATPase modulates exocytosis in neuroendocrine cells through the activation of the ARNO-Arf6-PLD pathway and the synthesis of phosphatidic acid |
| title_sort | v atpase modulates exocytosis in neuroendocrine cells through the activation of the arno arf6 pld pathway and the synthesis of phosphatidic acid |
| topic | chromaffin cells V-ATPase phospholipase D phospholipids neurosecretion membrane fusion |
| url | https://www.frontiersin.org/articles/10.3389/fmolb.2023.1163545/full |
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