Requirement of Cholesterol for Calcium‐Dependent Vesicle Fusion by Strengthening Synaptotagmin‐1‐Induced Membrane Bending
<p dir="ltr">Cholesterol is essential for neuronal activity and function. Cholesterol depletion in the plasma membrane impairs synaptic transmission. However, the molecular mechanisms by which cholesterol deficiency leads to defects in vesicle fusion remain poorly understood. Here, i...
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| المؤلف الرئيسي: | |
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| مؤلفون آخرون: | , , , , , |
| منشور في: |
2023
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| الموضوعات: | |
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| _version_ | 1864513511897432064 |
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| author | Houda Yasmine Ali Moussa (16855182) |
| author2 | Kyung Chul Shin (13913556) Janarthanan Ponraj (8535585) Soo Jin Kim (783747) Je‐Kyung Ryu (18877330) Said Mansour (8697699) Yongsoo Park (761850) |
| author2_role | author author author author author author |
| author_facet | Houda Yasmine Ali Moussa (16855182) Kyung Chul Shin (13913556) Janarthanan Ponraj (8535585) Soo Jin Kim (783747) Je‐Kyung Ryu (18877330) Said Mansour (8697699) Yongsoo Park (761850) |
| author_role | author |
| dc.creator.none.fl_str_mv | Houda Yasmine Ali Moussa (16855182) Kyung Chul Shin (13913556) Janarthanan Ponraj (8535585) Soo Jin Kim (783747) Je‐Kyung Ryu (18877330) Said Mansour (8697699) Yongsoo Park (761850) |
| dc.date.none.fl_str_mv | 2023-04-14T06:00:00Z |
| dc.identifier.none.fl_str_mv | 10.1002/advs.202206823 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/Requirement_of_Cholesterol_for_Calcium_Dependent_Vesicle_Fusion_by_Strengthening_Synaptotagmin_1_Induced_Membrane_Bending/26095240 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biological sciences Biochemistry and cell biology Biomedical and clinical sciences Medical physiology Neurosciences Cholesterol Neurodegeneration Neurogenesis Cholesterol depletion Amperometry |
| dc.title.none.fl_str_mv | Requirement of Cholesterol for Calcium‐Dependent Vesicle Fusion by Strengthening Synaptotagmin‐1‐Induced Membrane Bending |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <p dir="ltr">Cholesterol is essential for neuronal activity and function. Cholesterol depletion in the plasma membrane impairs synaptic transmission. However, the molecular mechanisms by which cholesterol deficiency leads to defects in vesicle fusion remain poorly understood. Here, it is shown that cholesterol is required for Ca2+‐dependent native vesicle fusion using the in vitro reconstitution of fusion and amperometry to monitor exocytosis in chromaffin cells. Purified native vesicles are crucial for the reconstitution of physiological Ca2+‐dependent fusion, because vesicle‐mimicking liposomes fail to reproduce the cholesterol effect. Intriguingly, cholesterol has no effect on the membrane binding of synaptotagmin‐1, a Ca2+ sensor for ultrafast fusion. Cholesterol strengthens local membrane deformation and bending induced by synaptotagmin‐1, thereby lowering the energy barrier for Ca2+‐dependent fusion to occur. The data provide evidence that cholesterol depletion abolishes Ca2+‐dependent vesicle fusion by disrupting synaptotagmin‐1‐induced membrane bending, and suggests that cholesterol is an essential lipid regulator for Ca2+‐dependent fusion.</p><h2>Other Information</h2><p dir="ltr">Published in: Advanced Science<br>License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1002/advs.202206823" target="_blank">https://dx.doi.org/10.1002/advs.202206823</a></p><p dir="ltr">Additional institutions affiliated with: Core Labs - QEERI</p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_cf05e7a3876178af60c4aa987056e986 |
| identifier_str_mv | 10.1002/advs.202206823 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/26095240 |
| publishDate | 2023 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Requirement of Cholesterol for Calcium‐Dependent Vesicle Fusion by Strengthening Synaptotagmin‐1‐Induced Membrane BendingHouda Yasmine Ali Moussa (16855182)Kyung Chul Shin (13913556)Janarthanan Ponraj (8535585)Soo Jin Kim (783747)Je‐Kyung Ryu (18877330)Said Mansour (8697699)Yongsoo Park (761850)Biological sciencesBiochemistry and cell biologyBiomedical and clinical sciencesMedical physiologyNeurosciencesCholesterolNeurodegenerationNeurogenesisCholesterol depletionAmperometry<p dir="ltr">Cholesterol is essential for neuronal activity and function. Cholesterol depletion in the plasma membrane impairs synaptic transmission. However, the molecular mechanisms by which cholesterol deficiency leads to defects in vesicle fusion remain poorly understood. Here, it is shown that cholesterol is required for Ca2+‐dependent native vesicle fusion using the in vitro reconstitution of fusion and amperometry to monitor exocytosis in chromaffin cells. Purified native vesicles are crucial for the reconstitution of physiological Ca2+‐dependent fusion, because vesicle‐mimicking liposomes fail to reproduce the cholesterol effect. Intriguingly, cholesterol has no effect on the membrane binding of synaptotagmin‐1, a Ca2+ sensor for ultrafast fusion. Cholesterol strengthens local membrane deformation and bending induced by synaptotagmin‐1, thereby lowering the energy barrier for Ca2+‐dependent fusion to occur. The data provide evidence that cholesterol depletion abolishes Ca2+‐dependent vesicle fusion by disrupting synaptotagmin‐1‐induced membrane bending, and suggests that cholesterol is an essential lipid regulator for Ca2+‐dependent fusion.</p><h2>Other Information</h2><p dir="ltr">Published in: Advanced Science<br>License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1002/advs.202206823" target="_blank">https://dx.doi.org/10.1002/advs.202206823</a></p><p dir="ltr">Additional institutions affiliated with: Core Labs - QEERI</p>2023-04-14T06:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1002/advs.202206823https://figshare.com/articles/journal_contribution/Requirement_of_Cholesterol_for_Calcium_Dependent_Vesicle_Fusion_by_Strengthening_Synaptotagmin_1_Induced_Membrane_Bending/26095240CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/260952402023-04-14T06:00:00Z |
| spellingShingle | Requirement of Cholesterol for Calcium‐Dependent Vesicle Fusion by Strengthening Synaptotagmin‐1‐Induced Membrane Bending Houda Yasmine Ali Moussa (16855182) Biological sciences Biochemistry and cell biology Biomedical and clinical sciences Medical physiology Neurosciences Cholesterol Neurodegeneration Neurogenesis Cholesterol depletion Amperometry |
| status_str | publishedVersion |
| title | Requirement of Cholesterol for Calcium‐Dependent Vesicle Fusion by Strengthening Synaptotagmin‐1‐Induced Membrane Bending |
| title_full | Requirement of Cholesterol for Calcium‐Dependent Vesicle Fusion by Strengthening Synaptotagmin‐1‐Induced Membrane Bending |
| title_fullStr | Requirement of Cholesterol for Calcium‐Dependent Vesicle Fusion by Strengthening Synaptotagmin‐1‐Induced Membrane Bending |
| title_full_unstemmed | Requirement of Cholesterol for Calcium‐Dependent Vesicle Fusion by Strengthening Synaptotagmin‐1‐Induced Membrane Bending |
| title_short | Requirement of Cholesterol for Calcium‐Dependent Vesicle Fusion by Strengthening Synaptotagmin‐1‐Induced Membrane Bending |
| title_sort | Requirement of Cholesterol for Calcium‐Dependent Vesicle Fusion by Strengthening Synaptotagmin‐1‐Induced Membrane Bending |
| topic | Biological sciences Biochemistry and cell biology Biomedical and clinical sciences Medical physiology Neurosciences Cholesterol Neurodegeneration Neurogenesis Cholesterol depletion Amperometry |