ANXA11 biomolecular condensates facilitate protein-lipid phase coupling on lysosomal membranes
Abstract Phase transitions of cellular proteins and lipids play a key role in governing the organisation and coordination of intracellular biology. Recent work has raised the intriguing prospect that phase transitions in proteins and lipids can be co-regulated. Here we investigate this possibility i...
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Nature Portfolio
2025-03-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-58142-5 |
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| author | Jonathon Nixon-Abell Francesco S. Ruggeri Seema Qamar Therese W. Herling Magdalena A. Czekalska Yi Shen Guozhen Wang Christopher King Michael S. Fernandopulle Tomas Sneideris Joseph L. Watson Visakh V. S. Pillai William Meadows James W. Henderson Joseph E. Chambers Jane L. Wagstaff Sioned H. Williams Helena Coyle Greta Šneiderienė Yuqian Lu Shuyuan Zhang Stefan J. Marciniak Stefan M. V. Freund Emmanuel Derivery Michael E. Ward Michele Vendruscolo Tuomas P. J. Knowles Peter St George-Hyslop |
| author_facet | Jonathon Nixon-Abell Francesco S. Ruggeri Seema Qamar Therese W. Herling Magdalena A. Czekalska Yi Shen Guozhen Wang Christopher King Michael S. Fernandopulle Tomas Sneideris Joseph L. Watson Visakh V. S. Pillai William Meadows James W. Henderson Joseph E. Chambers Jane L. Wagstaff Sioned H. Williams Helena Coyle Greta Šneiderienė Yuqian Lu Shuyuan Zhang Stefan J. Marciniak Stefan M. V. Freund Emmanuel Derivery Michael E. Ward Michele Vendruscolo Tuomas P. J. Knowles Peter St George-Hyslop |
| author_sort | Jonathon Nixon-Abell |
| collection | DOAJ |
| description | Abstract Phase transitions of cellular proteins and lipids play a key role in governing the organisation and coordination of intracellular biology. Recent work has raised the intriguing prospect that phase transitions in proteins and lipids can be co-regulated. Here we investigate this possibility in the ribonucleoprotein (RNP) granule-ANXA11-lysosome ensemble, where ANXA11 tethers RNP granules to lysosomal membranes to enable their co-trafficking. We show that changes to the protein phase state within this system, driven by the low complexity ANXA11 N-terminus, induces a coupled phase state change in the lipids of the underlying membrane. We identify the ANXA11 interacting proteins ALG2 and CALC as potent regulators of ANXA11-based phase coupling and demonstrate their influence on the nanomechanical properties of the ANXA11-lysosome ensemble and its capacity to engage RNP granules. The phenomenon of protein-lipid phase coupling we observe within this system serves as a potential regulatory mechanism in RNA trafficking and offers an important template to understand other examples across the cell whereby biomolecular condensates closely juxtapose organellar membranes. |
| format | Article |
| id | doaj-art-32cf764c6d3b4089a1ce73485d879d8c |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-32cf764c6d3b4089a1ce73485d879d8c2025-08-20T03:41:42ZengNature PortfolioNature Communications2041-17232025-03-0116111910.1038/s41467-025-58142-5ANXA11 biomolecular condensates facilitate protein-lipid phase coupling on lysosomal membranesJonathon Nixon-Abell0Francesco S. Ruggeri1Seema Qamar2Therese W. Herling3Magdalena A. Czekalska4Yi Shen5Guozhen Wang6Christopher King7Michael S. Fernandopulle8Tomas Sneideris9Joseph L. Watson10Visakh V. S. Pillai11William Meadows12James W. Henderson13Joseph E. Chambers14Jane L. Wagstaff15Sioned H. Williams16Helena Coyle17Greta Šneiderienė18Yuqian Lu19Shuyuan Zhang20Stefan J. Marciniak21Stefan M. V. Freund22Emmanuel Derivery23Michael E. Ward24Michele Vendruscolo25Tuomas P. J. Knowles26Peter St George-Hyslop27Department of Clinical Neurosciences, Cambridge Institute for Medical Research, Clinical School, University of CambridgePhysical Chemistry and Soft matter, Wageningen University & ResearchDepartment of Clinical Neurosciences, Cambridge Institute for Medical Research, Clinical School, University of CambridgeYusuf Hamied Department of Chemistry, Centre for Misfolding Diseases, University of CambridgeYusuf Hamied Department of Chemistry, Centre for Misfolding Diseases, University of CambridgeYusuf Hamied Department of Chemistry, Centre for Misfolding Diseases, University of CambridgeDepartment of Clinical Neurosciences, Cambridge Institute for Medical Research, Clinical School, University of CambridgeNational institute for Neurological Disorder and Stroke, NIHDepartment of Clinical Neurosciences, Cambridge Institute for Medical Research, Clinical School, University of CambridgeYusuf Hamied Department of Chemistry, Centre for Misfolding Diseases, University of CambridgeCell Biology Division, MRC Laboratory of Molecular BiologyPhysical Chemistry and Soft matter, Wageningen University & ResearchDepartment of Clinical Neurosciences, Cambridge Institute for Medical Research, Clinical School, University of CambridgeDepartment of Clinical Neurosciences, Cambridge Institute for Medical Research, Clinical School, University of CambridgeDepartment of Clinical Neurosciences, Cambridge Institute for Medical Research, Clinical School, University of CambridgeStructure Studies Division, NMR Facility, MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge Biomedical CampusDepartment of Clinical Neurosciences, Cambridge Institute for Medical Research, Clinical School, University of CambridgeDepartment of Clinical Neurosciences, Cambridge Institute for Medical Research, Clinical School, University of CambridgeYusuf Hamied Department of Chemistry, Centre for Misfolding Diseases, University of CambridgeYusuf Hamied Department of Chemistry, Centre for Misfolding Diseases, University of CambridgeYusuf Hamied Department of Chemistry, Centre for Misfolding Diseases, University of CambridgeDepartment of Clinical Neurosciences, Cambridge Institute for Medical Research, Clinical School, University of CambridgeStructure Studies Division, NMR Facility, MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge Biomedical CampusCell Biology Division, MRC Laboratory of Molecular BiologyNational institute for Neurological Disorder and Stroke, NIHYusuf Hamied Department of Chemistry, Centre for Misfolding Diseases, University of CambridgeYusuf Hamied Department of Chemistry, Centre for Misfolding Diseases, University of CambridgeDepartment of Medicine (Division of Neurology), Temerty Faculty of Medicine, University Health Network, University of TorontoAbstract Phase transitions of cellular proteins and lipids play a key role in governing the organisation and coordination of intracellular biology. Recent work has raised the intriguing prospect that phase transitions in proteins and lipids can be co-regulated. Here we investigate this possibility in the ribonucleoprotein (RNP) granule-ANXA11-lysosome ensemble, where ANXA11 tethers RNP granules to lysosomal membranes to enable their co-trafficking. We show that changes to the protein phase state within this system, driven by the low complexity ANXA11 N-terminus, induces a coupled phase state change in the lipids of the underlying membrane. We identify the ANXA11 interacting proteins ALG2 and CALC as potent regulators of ANXA11-based phase coupling and demonstrate their influence on the nanomechanical properties of the ANXA11-lysosome ensemble and its capacity to engage RNP granules. The phenomenon of protein-lipid phase coupling we observe within this system serves as a potential regulatory mechanism in RNA trafficking and offers an important template to understand other examples across the cell whereby biomolecular condensates closely juxtapose organellar membranes.https://doi.org/10.1038/s41467-025-58142-5 |
| spellingShingle | Jonathon Nixon-Abell Francesco S. Ruggeri Seema Qamar Therese W. Herling Magdalena A. Czekalska Yi Shen Guozhen Wang Christopher King Michael S. Fernandopulle Tomas Sneideris Joseph L. Watson Visakh V. S. Pillai William Meadows James W. Henderson Joseph E. Chambers Jane L. Wagstaff Sioned H. Williams Helena Coyle Greta Šneiderienė Yuqian Lu Shuyuan Zhang Stefan J. Marciniak Stefan M. V. Freund Emmanuel Derivery Michael E. Ward Michele Vendruscolo Tuomas P. J. Knowles Peter St George-Hyslop ANXA11 biomolecular condensates facilitate protein-lipid phase coupling on lysosomal membranes Nature Communications |
| title | ANXA11 biomolecular condensates facilitate protein-lipid phase coupling on lysosomal membranes |
| title_full | ANXA11 biomolecular condensates facilitate protein-lipid phase coupling on lysosomal membranes |
| title_fullStr | ANXA11 biomolecular condensates facilitate protein-lipid phase coupling on lysosomal membranes |
| title_full_unstemmed | ANXA11 biomolecular condensates facilitate protein-lipid phase coupling on lysosomal membranes |
| title_short | ANXA11 biomolecular condensates facilitate protein-lipid phase coupling on lysosomal membranes |
| title_sort | anxa11 biomolecular condensates facilitate protein lipid phase coupling on lysosomal membranes |
| url | https://doi.org/10.1038/s41467-025-58142-5 |
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