Structure modeling hints at a granular organization of the Golgi ribbon
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2022 |
| Outros Autores: | , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
| Texto Completo: | http://hdl.handle.net/10362/143869 |
Resumo: | Funding Information: This work was funded by the Medical Research Council (grants MC_UU_12018/2 and MC_UU_00012/2 to D.F.C.) and by the British Heart Foundation (grant PG/14/76/31087 to D.F.C.). Publisher Copyright: © 2022, The Author(s). |
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Structure modeling hints at a granular organization of the Golgi ribbonGolgi apparatusGolgi ribbonMathematical modelingOrganelle structureWeibel-Palade bodyBiotechnologyStructural BiologyEcology, Evolution, Behavior and SystematicsPhysiologyBiochemistry, Genetics and Molecular Biology(all)Agricultural and Biological Sciences(all)Plant ScienceDevelopmental BiologyCell BiologyFunding Information: This work was funded by the Medical Research Council (grants MC_UU_12018/2 and MC_UU_00012/2 to D.F.C.) and by the British Heart Foundation (grant PG/14/76/31087 to D.F.C.). Publisher Copyright: © 2022, The Author(s).Background: In vertebrate cells, the Golgi functional subunits, mini-stacks, are linked into a tri-dimensional network. How this “ribbon” architecture relates to Golgi functions remains unclear. Are all connections between mini-stacks equal? Is the local structure of the ribbon of functional importance? These are difficult questions to address, without a quantifiable readout of the output of ribbon-embedded mini-stacks. Endothelial cells produce secretory granules, the Weibel-Palade bodies (WPB), whose von Willebrand Factor (VWF) cargo is central to hemostasis. The Golgi apparatus controls WPB size at both mini-stack and ribbon levels. Mini-stack dimensions delimit the size of VWF "boluses” whilst the ribbon architecture allows their linear co-packaging, thereby generating WPBs of different lengths. This Golgi/WPB size relationship suits mathematical analysis. Results: WPB lengths were quantized as multiples of the bolus size and mathematical modeling simulated the effects of different Golgi ribbon organizations on WPB size, to be compared with the ground truth of experimental data. An initial simple model, with the Golgi as a single long ribbon composed of linearly interlinked mini-stacks, was refined to a collection of mini-ribbons and then to a mixture of mini-stack dimers plus long ribbon segments. Complementing these models with cell culture experiments led to novel findings. Firstly, one-bolus sized WPBs are secreted faster than larger secretory granules. Secondly, microtubule depolymerization unlinks the Golgi into equal proportions of mini-stack monomers and dimers. Kinetics of binding/unbinding of mini-stack monomers underpinning the presence of stable dimers was then simulated. Assuming that stable mini-stack dimers and monomers persist within the ribbon resulted in a final model that predicts a “breathing” arrangement of the Golgi, where monomer and dimer mini-stacks within longer structures undergo continuous linking/unlinking, consistent with experimentally observed WPB size distributions. Conclusions: Hypothetical Golgi organizations were validated against a quantifiable secretory output. The best-fitting Golgi model, accounting for stable mini-stack dimers, is consistent with a highly dynamic ribbon structure, capable of rapid rearrangement. Our modeling exercise therefore predicts that at the fine-grained level the Golgi ribbon is more complex than generally thought. Future experiments will confirm whether such a ribbon organization is endothelial-specific or a general feature of vertebrate cells.NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)iNOVA4Health - pólo NMSCentro de Estudos de Doenças Crónicas (CEDOC)RUNPage, Karen M.McCormack, Jessica J.Lopes-da-Silva, MafaldaPatella, FrancescaHarrison-Lavoie, KimberlyBurden, Jemima J.Quah, Ying Yi BernadetteScaglioni, DominicFerraro, FrancescoCutler, Daniel F.2022-09-20T22:26:11Z2022-05-132022-05-13T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10362/143869eng1741-7007PURE: 46652052https://doi.org/10.1186/s12915-022-01305-3info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-03-11T05:22:43Zoai:run.unl.pt:10362/143869Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:51:11.072008Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
| dc.title.none.fl_str_mv |
Structure modeling hints at a granular organization of the Golgi ribbon |
| title |
Structure modeling hints at a granular organization of the Golgi ribbon |
| spellingShingle |
Structure modeling hints at a granular organization of the Golgi ribbon Page, Karen M. Golgi apparatus Golgi ribbon Mathematical modeling Organelle structure Weibel-Palade body Biotechnology Structural Biology Ecology, Evolution, Behavior and Systematics Physiology Biochemistry, Genetics and Molecular Biology(all) Agricultural and Biological Sciences(all) Plant Science Developmental Biology Cell Biology |
| title_short |
Structure modeling hints at a granular organization of the Golgi ribbon |
| title_full |
Structure modeling hints at a granular organization of the Golgi ribbon |
| title_fullStr |
Structure modeling hints at a granular organization of the Golgi ribbon |
| title_full_unstemmed |
Structure modeling hints at a granular organization of the Golgi ribbon |
| title_sort |
Structure modeling hints at a granular organization of the Golgi ribbon |
| author |
Page, Karen M. |
| author_facet |
Page, Karen M. McCormack, Jessica J. Lopes-da-Silva, Mafalda Patella, Francesca Harrison-Lavoie, Kimberly Burden, Jemima J. Quah, Ying Yi Bernadette Scaglioni, Dominic Ferraro, Francesco Cutler, Daniel F. |
| author_role |
author |
| author2 |
McCormack, Jessica J. Lopes-da-Silva, Mafalda Patella, Francesca Harrison-Lavoie, Kimberly Burden, Jemima J. Quah, Ying Yi Bernadette Scaglioni, Dominic Ferraro, Francesco Cutler, Daniel F. |
| author2_role |
author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM) iNOVA4Health - pólo NMS Centro de Estudos de Doenças Crónicas (CEDOC) RUN |
| dc.contributor.author.fl_str_mv |
Page, Karen M. McCormack, Jessica J. Lopes-da-Silva, Mafalda Patella, Francesca Harrison-Lavoie, Kimberly Burden, Jemima J. Quah, Ying Yi Bernadette Scaglioni, Dominic Ferraro, Francesco Cutler, Daniel F. |
| dc.subject.por.fl_str_mv |
Golgi apparatus Golgi ribbon Mathematical modeling Organelle structure Weibel-Palade body Biotechnology Structural Biology Ecology, Evolution, Behavior and Systematics Physiology Biochemistry, Genetics and Molecular Biology(all) Agricultural and Biological Sciences(all) Plant Science Developmental Biology Cell Biology |
| topic |
Golgi apparatus Golgi ribbon Mathematical modeling Organelle structure Weibel-Palade body Biotechnology Structural Biology Ecology, Evolution, Behavior and Systematics Physiology Biochemistry, Genetics and Molecular Biology(all) Agricultural and Biological Sciences(all) Plant Science Developmental Biology Cell Biology |
| description |
Funding Information: This work was funded by the Medical Research Council (grants MC_UU_12018/2 and MC_UU_00012/2 to D.F.C.) and by the British Heart Foundation (grant PG/14/76/31087 to D.F.C.). Publisher Copyright: © 2022, The Author(s). |
| publishDate |
2022 |
| dc.date.none.fl_str_mv |
2022-09-20T22:26:11Z 2022-05-13 2022-05-13T00:00:00Z |
| dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
| dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
| format |
article |
| status_str |
publishedVersion |
| dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10362/143869 |
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http://hdl.handle.net/10362/143869 |
| dc.language.iso.fl_str_mv |
eng |
| language |
eng |
| dc.relation.none.fl_str_mv |
1741-7007 PURE: 46652052 https://doi.org/10.1186/s12915-022-01305-3 |
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info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
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reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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