Plasma membrane remodeling determines adipocyte expansion and mechanical adaptability
Abstract Adipocytes expand massively to accommodate excess energy stores and protect the organism from lipotoxicity. Adipose tissue expandability is at the center of disorders such as obesity and lipodystrophy; however, little is known about the relevance of adipocyte biomechanics on the etiology of...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-11-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-54224-y |
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| author | María C. M. Aboy-Pardal Marta C. Guadamillas Carlos R. Guerrero Mauro Català-Montoro Mónica Toledano-Donado Sara Terrés-Domínguez Dácil M. Pavón Víctor Jiménez-Jiménez Daniel Jimenez-Carretero Moreno Zamai Cintia Folgueira Ana Cerezo Fidel-Nicolás Lolo Rubén Nogueiras Guadalupe Sabio Miguel Sánchez-Álvarez Asier Echarri Ricardo Garcia Miguel A. Del Pozo |
| author_facet | María C. M. Aboy-Pardal Marta C. Guadamillas Carlos R. Guerrero Mauro Català-Montoro Mónica Toledano-Donado Sara Terrés-Domínguez Dácil M. Pavón Víctor Jiménez-Jiménez Daniel Jimenez-Carretero Moreno Zamai Cintia Folgueira Ana Cerezo Fidel-Nicolás Lolo Rubén Nogueiras Guadalupe Sabio Miguel Sánchez-Álvarez Asier Echarri Ricardo Garcia Miguel A. Del Pozo |
| author_sort | María C. M. Aboy-Pardal |
| collection | DOAJ |
| description | Abstract Adipocytes expand massively to accommodate excess energy stores and protect the organism from lipotoxicity. Adipose tissue expandability is at the center of disorders such as obesity and lipodystrophy; however, little is known about the relevance of adipocyte biomechanics on the etiology of these conditions. Here, we show in male mice in vivo that the adipocyte plasma membrane undergoes caveolar domain reorganization upon lipid droplet expansion. As the lipid droplet grows, caveolae disassemble to release their membrane reservoir and increase cell surface area, and transfer specific caveolar components to the LD surface. Adipose tissue null for caveolae is stiffer, shows compromised deformability, and is prone to rupture under mechanical compression. Mechanistically, phosphoacceptor Cav1 Tyr14 is required for caveolae disassembly: adipocytes bearing a Tyr14Phe mutation at this residue are stiffer and smaller, leading to decreased adiposity in vivo; exhibit deficient transfer of Cav1 and EHD2 to the LD surface, and show distinct Cav1 molecular dynamics and tension adaptation. These results indicate that Cav1 phosphoregulation modulates caveolar dynamics as a relevant component of the homeostatic mechanoadaptation of the differentiated adipocyte. |
| format | Article |
| id | doaj-art-67c1dc358d36404a815842f71018ebb3 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-67c1dc358d36404a815842f71018ebb32024-12-01T12:35:43ZengNature PortfolioNature Communications2041-17232024-11-0115112710.1038/s41467-024-54224-yPlasma membrane remodeling determines adipocyte expansion and mechanical adaptabilityMaría C. M. Aboy-Pardal0Marta C. Guadamillas1Carlos R. Guerrero2Mauro Català-Montoro3Mónica Toledano-Donado4Sara Terrés-Domínguez5Dácil M. Pavón6Víctor Jiménez-Jiménez7Daniel Jimenez-Carretero8Moreno Zamai9Cintia Folgueira10Ana Cerezo11Fidel-Nicolás Lolo12Rubén Nogueiras13Guadalupe Sabio14Miguel Sánchez-Álvarez15Asier Echarri16Ricardo Garcia17Miguel A. Del Pozo18Mechanoadaptation and Caveolae Biology lab, Novel mechanisms in atherosclerosis program. Centro Nacional de Investigaciones Cardiovasculares (CNIC)Mechanoadaptation and Caveolae Biology lab, Novel mechanisms in atherosclerosis program. Centro Nacional de Investigaciones Cardiovasculares (CNIC)ForceTool group, Instituto de Ciencia de Materiales de Madrid (ICMM), CSICMechanoadaptation and Caveolae Biology lab, Novel mechanisms in atherosclerosis program. Centro Nacional de Investigaciones Cardiovasculares (CNIC)Mechanoadaptation and Caveolae Biology lab, Novel mechanisms in atherosclerosis program. Centro Nacional de Investigaciones Cardiovasculares (CNIC)Mechanoadaptation and Caveolae Biology lab, Novel mechanisms in atherosclerosis program. Centro Nacional de Investigaciones Cardiovasculares (CNIC)Mechanoadaptation and Caveolae Biology lab, Novel mechanisms in atherosclerosis program. Centro Nacional de Investigaciones Cardiovasculares (CNIC)Mechanoadaptation and Caveolae Biology lab, Novel mechanisms in atherosclerosis program. Centro Nacional de Investigaciones Cardiovasculares (CNIC)Cellomics Unit, Cell and Developmental Biology Area. Centro Nacional de Investigaciones Cardiovasculares (CNIC)Microscopy and Dynamic Imaging Unit, Centro Nacional de Investigaciones Cardiovasculares (CNIC)Centro de Investigación en Medicina Molecular y Enfermedades Crónicas CIMUSMechanoadaptation and Caveolae Biology lab, Novel mechanisms in atherosclerosis program. Centro Nacional de Investigaciones Cardiovasculares (CNIC)Mechanoadaptation and Caveolae Biology lab, Novel mechanisms in atherosclerosis program. Centro Nacional de Investigaciones Cardiovasculares (CNIC)Centro de Investigación en Medicina Molecular y Enfermedades Crónicas CIMUSStress kinases in Diabetes, Cancer and Cardiovascular Disease lab. Cardiovascular risk factors & brain function program, Centro Nacional de Investigaciones Cardiovasculares (CNIC)Mechanoadaptation and Caveolae Biology lab, Novel mechanisms in atherosclerosis program. Centro Nacional de Investigaciones Cardiovasculares (CNIC)Mechanoadaptation and Caveolae Biology lab, Novel mechanisms in atherosclerosis program. Centro Nacional de Investigaciones Cardiovasculares (CNIC)ForceTool group, Instituto de Ciencia de Materiales de Madrid (ICMM), CSICMechanoadaptation and Caveolae Biology lab, Novel mechanisms in atherosclerosis program. Centro Nacional de Investigaciones Cardiovasculares (CNIC)Abstract Adipocytes expand massively to accommodate excess energy stores and protect the organism from lipotoxicity. Adipose tissue expandability is at the center of disorders such as obesity and lipodystrophy; however, little is known about the relevance of adipocyte biomechanics on the etiology of these conditions. Here, we show in male mice in vivo that the adipocyte plasma membrane undergoes caveolar domain reorganization upon lipid droplet expansion. As the lipid droplet grows, caveolae disassemble to release their membrane reservoir and increase cell surface area, and transfer specific caveolar components to the LD surface. Adipose tissue null for caveolae is stiffer, shows compromised deformability, and is prone to rupture under mechanical compression. Mechanistically, phosphoacceptor Cav1 Tyr14 is required for caveolae disassembly: adipocytes bearing a Tyr14Phe mutation at this residue are stiffer and smaller, leading to decreased adiposity in vivo; exhibit deficient transfer of Cav1 and EHD2 to the LD surface, and show distinct Cav1 molecular dynamics and tension adaptation. These results indicate that Cav1 phosphoregulation modulates caveolar dynamics as a relevant component of the homeostatic mechanoadaptation of the differentiated adipocyte.https://doi.org/10.1038/s41467-024-54224-y |
| spellingShingle | María C. M. Aboy-Pardal Marta C. Guadamillas Carlos R. Guerrero Mauro Català-Montoro Mónica Toledano-Donado Sara Terrés-Domínguez Dácil M. Pavón Víctor Jiménez-Jiménez Daniel Jimenez-Carretero Moreno Zamai Cintia Folgueira Ana Cerezo Fidel-Nicolás Lolo Rubén Nogueiras Guadalupe Sabio Miguel Sánchez-Álvarez Asier Echarri Ricardo Garcia Miguel A. Del Pozo Plasma membrane remodeling determines adipocyte expansion and mechanical adaptability Nature Communications |
| title | Plasma membrane remodeling determines adipocyte expansion and mechanical adaptability |
| title_full | Plasma membrane remodeling determines adipocyte expansion and mechanical adaptability |
| title_fullStr | Plasma membrane remodeling determines adipocyte expansion and mechanical adaptability |
| title_full_unstemmed | Plasma membrane remodeling determines adipocyte expansion and mechanical adaptability |
| title_short | Plasma membrane remodeling determines adipocyte expansion and mechanical adaptability |
| title_sort | plasma membrane remodeling determines adipocyte expansion and mechanical adaptability |
| url | https://doi.org/10.1038/s41467-024-54224-y |
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