Structure modeling hints at a granular organization of the Golgi ribbon
Abstract 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...
| Main Authors: | , , , , , , , , , |
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| Language: | English |
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BMC
2022-05-01
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| Series: | BMC Biology |
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| Online Access: | https://doi.org/10.1186/s12915-022-01305-3 |
| _version_ | 1828793000122122240 |
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| author | Karen M. Page Jessica J. McCormack Mafalda Lopes-da-Silva Francesca Patella Kimberly Harrison-Lavoie Jemima J. Burden Ying-Yi Bernadette Quah Dominic Scaglioni Francesco Ferraro Daniel F. Cutler |
| author_facet | Karen M. Page Jessica J. McCormack Mafalda Lopes-da-Silva Francesca Patella Kimberly Harrison-Lavoie Jemima J. Burden Ying-Yi Bernadette Quah Dominic Scaglioni Francesco Ferraro Daniel F. Cutler |
| author_sort | Karen M. Page |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-12-12T03:19:46Z |
| format | Article |
| id | doaj.art-ea370c24b3234d728be9cf0d1e4f597f |
| institution | Directory Open Access Journal |
| issn | 1741-7007 |
| language | English |
| last_indexed | 2024-12-12T03:19:46Z |
| publishDate | 2022-05-01 |
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| spelling | doaj.art-ea370c24b3234d728be9cf0d1e4f597f2022-12-22T00:40:12ZengBMCBMC Biology1741-70072022-05-0120111610.1186/s12915-022-01305-3Structure modeling hints at a granular organization of the Golgi ribbonKaren M. Page0Jessica J. McCormack1Mafalda Lopes-da-Silva2Francesca Patella3Kimberly Harrison-Lavoie4Jemima J. Burden5Ying-Yi Bernadette Quah6Dominic Scaglioni7Francesco Ferraro8Daniel F. Cutler9Department of Mathematics, University College LondonMRC Laboratory for Molecular cell Biology, University College LondonMRC Laboratory for Molecular cell Biology, University College LondonMRC Laboratory for Molecular cell Biology, University College LondonMRC Laboratory for Molecular cell Biology, University College LondonMRC Laboratory for Molecular cell Biology, University College LondonMRC Laboratory for Molecular cell Biology, University College LondonMRC Laboratory for Molecular cell Biology, University College LondonDepartment of Biology and Evolution of Marine Organisms, BEOM, Stazione Zoologica Anton DohrnMRC Laboratory for Molecular cell Biology, University College LondonAbstract 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.https://doi.org/10.1186/s12915-022-01305-3Golgi apparatusGolgi ribbonOrganelle structureWeibel-Palade bodyMathematical modeling |
| spellingShingle | Karen M. Page Jessica J. McCormack Mafalda Lopes-da-Silva Francesca Patella Kimberly Harrison-Lavoie Jemima J. Burden Ying-Yi Bernadette Quah Dominic Scaglioni Francesco Ferraro Daniel F. Cutler Structure modeling hints at a granular organization of the Golgi ribbon BMC Biology Golgi apparatus Golgi ribbon Organelle structure Weibel-Palade body Mathematical modeling |
| title | 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_short | Structure modeling hints at a granular organization of the Golgi ribbon |
| title_sort | structure modeling hints at a granular organization of the golgi ribbon |
| topic | Golgi apparatus Golgi ribbon Organelle structure Weibel-Palade body Mathematical modeling |
| url | https://doi.org/10.1186/s12915-022-01305-3 |
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