Atypical peripheral actin band formation via overactivation of RhoA and nonmuscle myosin II in mitofusin 2-deficient cells
Cell spreading and migration play central roles in many physiological and pathophysiological processes. We have previously shown that MFN2 regulates the migration of human neutrophil-like cells via suppressing Rac activation. Here, we show that in mouse embryonic fibroblasts, MFN2 suppresses RhoA ac...
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eLife Sciences Publications Ltd
2023-09-01
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| Online Access: | https://elifesciences.org/articles/88828 |
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| author | Yueyang Wang Lee D Troughton Fan Xu Aritra Chatterjee Chang Ding Han Zhao Laura Pulido Cifuentes Ryan B Wagner Tianqi Wang Shelly Tan Jingjuan Chen Linlin Li David Umulis Shihuan Kuang Daniel M Suter Chongli Yuan Deva Chan Fang Huang Patrick W Oakes Qing Deng |
| author_facet | Yueyang Wang Lee D Troughton Fan Xu Aritra Chatterjee Chang Ding Han Zhao Laura Pulido Cifuentes Ryan B Wagner Tianqi Wang Shelly Tan Jingjuan Chen Linlin Li David Umulis Shihuan Kuang Daniel M Suter Chongli Yuan Deva Chan Fang Huang Patrick W Oakes Qing Deng |
| author_sort | Yueyang Wang |
| collection | DOAJ |
| description | Cell spreading and migration play central roles in many physiological and pathophysiological processes. We have previously shown that MFN2 regulates the migration of human neutrophil-like cells via suppressing Rac activation. Here, we show that in mouse embryonic fibroblasts, MFN2 suppresses RhoA activation and supports cell polarization. After initial spreading, the wild-type cells polarize and migrate, whereas the Mfn2-/- cells maintain a circular shape. Increased cytosolic Ca2+ resulting from the loss of Mfn2 is directly responsible for this phenotype, which can be rescued by expressing an artificial tether to bring mitochondria and endoplasmic reticulum to close vicinity. Elevated cytosolic Ca2+ activates Ca2+/calmodulin-dependent protein kinase II, RhoA, and myosin light-chain kinase, causing an overactivation of nonmuscle myosin II, leading to a formation of a prominent F-actin ring at the cell periphery and increased cell contractility. The peripheral actin band alters cell physics and is dependent on substrate rigidity. Our results provide a novel molecular basis to understand how MFN2 regulates distinct signaling pathways in different cells and tissue environments, which is instrumental in understanding and treating MFN2-related diseases. |
| format | Article |
| id | doaj-art-80d2f4bf1af140f981ecc2ce933a1e23 |
| institution | Matheson Library |
| issn | 2050-084X |
| language | English |
| publishDate | 2023-09-01 |
| publisher | eLife Sciences Publications Ltd |
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| series | eLife |
| spelling | doaj-art-80d2f4bf1af140f981ecc2ce933a1e232025-07-15T14:37:51ZengeLife Sciences Publications LtdeLife2050-084X2023-09-011210.7554/eLife.88828Atypical peripheral actin band formation via overactivation of RhoA and nonmuscle myosin II in mitofusin 2-deficient cellsYueyang Wang0https://orcid.org/0000-0002-5445-8186Lee D Troughton1Fan Xu2https://orcid.org/0000-0001-6298-5587Aritra Chatterjee3https://orcid.org/0000-0002-5318-3459Chang Ding4Han Zhao5Laura Pulido Cifuentes6Ryan B Wagner7https://orcid.org/0000-0002-4111-8027Tianqi Wang8Shelly Tan9Jingjuan Chen10Linlin Li11https://orcid.org/0000-0002-9667-2965David Umulis12https://orcid.org/0000-0003-1913-2284Shihuan Kuang13https://orcid.org/0000-0001-9180-3180Daniel M Suter14https://orcid.org/0000-0002-5230-7229Chongli Yuan15https://orcid.org/0000-0003-3765-0931Deva Chan16https://orcid.org/0000-0003-1508-1045Fang Huang17Patrick W Oakes18https://orcid.org/0000-0001-9951-1318Qing Deng19https://orcid.org/0000-0002-9254-9951Department of Biological Sciences, Purdue University West Lafayette, West Lafayette, United StatesCell and Molecular Physiology, Loyola University Chicago, Chicago, United StatesWeldon School of Biomedical Engineering, Purdue University West Lafayette, West Lafayette, United States; Advanced Research Institute of Multidisciplinary Science, Beijing Institute of Technology, Beijing, ChinaWeldon School of Biomedical Engineering, Purdue University West Lafayette, West Lafayette, United StatesDepartment of Biological Sciences, Purdue University West Lafayette, West Lafayette, United StatesDavidson School of Chemical Engineering, Purdue University West Lafayette, West Lafayette, United StatesDepartment of Biological Sciences, Purdue University West Lafayette, West Lafayette, United StatesSchool of Mechanical Engineering, Purdue University West Lafayette, West Lafayette, United StatesDepartment of Biological Sciences, Purdue University West Lafayette, West Lafayette, United StatesDepartment of Biological Sciences, Purdue University West Lafayette, West Lafayette, United StatesDepartment of Animal Sciences, Purdue University West Lafayette, West Lafayette, United StatesWeldon School of Biomedical Engineering, Purdue University West Lafayette, West Lafayette, United StatesWeldon School of Biomedical Engineering, Purdue University West Lafayette, West Lafayette, United States; Department of Agricultural and Biological Engineering, Purdue University West Lafayette, West Lafayette, United StatesDepartment of Animal Sciences, Purdue University West Lafayette, West Lafayette, United StatesDepartment of Biological Sciences, Purdue University West Lafayette, West Lafayette, United States; Purdue Institute for Integrative Neuroscience, Purdue University West Lafayette, West Lafayette, United States; Purdue Institute for Inflammation, Immunology & Infectious Disease, Purdue University West Lafayette, West Lafayette, United StatesDavidson School of Chemical Engineering, Purdue University West Lafayette, West Lafayette, United StatesWeldon School of Biomedical Engineering, Purdue University West Lafayette, West Lafayette, United StatesWeldon School of Biomedical Engineering, Purdue University West Lafayette, West Lafayette, United StatesCell and Molecular Physiology, Loyola University Chicago, Chicago, United StatesDepartment of Biological Sciences, Purdue University West Lafayette, West Lafayette, United States; Purdue Institute for Inflammation, Immunology & Infectious Disease, Purdue University West Lafayette, West Lafayette, United States; Purdue University Center for Cancer Research, Purdue University West Lafayette, West Lafayette, United StatesCell spreading and migration play central roles in many physiological and pathophysiological processes. We have previously shown that MFN2 regulates the migration of human neutrophil-like cells via suppressing Rac activation. Here, we show that in mouse embryonic fibroblasts, MFN2 suppresses RhoA activation and supports cell polarization. After initial spreading, the wild-type cells polarize and migrate, whereas the Mfn2-/- cells maintain a circular shape. Increased cytosolic Ca2+ resulting from the loss of Mfn2 is directly responsible for this phenotype, which can be rescued by expressing an artificial tether to bring mitochondria and endoplasmic reticulum to close vicinity. Elevated cytosolic Ca2+ activates Ca2+/calmodulin-dependent protein kinase II, RhoA, and myosin light-chain kinase, causing an overactivation of nonmuscle myosin II, leading to a formation of a prominent F-actin ring at the cell periphery and increased cell contractility. The peripheral actin band alters cell physics and is dependent on substrate rigidity. Our results provide a novel molecular basis to understand how MFN2 regulates distinct signaling pathways in different cells and tissue environments, which is instrumental in understanding and treating MFN2-related diseases.https://elifesciences.org/articles/88828cell spreadingcell migrationmitochondrial-ER tetherRho GTPasecalcium signalingmouse embryonic fibroblasts |
| spellingShingle | Yueyang Wang Lee D Troughton Fan Xu Aritra Chatterjee Chang Ding Han Zhao Laura Pulido Cifuentes Ryan B Wagner Tianqi Wang Shelly Tan Jingjuan Chen Linlin Li David Umulis Shihuan Kuang Daniel M Suter Chongli Yuan Deva Chan Fang Huang Patrick W Oakes Qing Deng Atypical peripheral actin band formation via overactivation of RhoA and nonmuscle myosin II in mitofusin 2-deficient cells eLife cell spreading cell migration mitochondrial-ER tether Rho GTPase calcium signaling mouse embryonic fibroblasts |
| title | Atypical peripheral actin band formation via overactivation of RhoA and nonmuscle myosin II in mitofusin 2-deficient cells |
| title_full | Atypical peripheral actin band formation via overactivation of RhoA and nonmuscle myosin II in mitofusin 2-deficient cells |
| title_fullStr | Atypical peripheral actin band formation via overactivation of RhoA and nonmuscle myosin II in mitofusin 2-deficient cells |
| title_full_unstemmed | Atypical peripheral actin band formation via overactivation of RhoA and nonmuscle myosin II in mitofusin 2-deficient cells |
| title_short | Atypical peripheral actin band formation via overactivation of RhoA and nonmuscle myosin II in mitofusin 2-deficient cells |
| title_sort | atypical peripheral actin band formation via overactivation of rhoa and nonmuscle myosin ii in mitofusin 2 deficient cells |
| topic | cell spreading cell migration mitochondrial-ER tether Rho GTPase calcium signaling mouse embryonic fibroblasts |
| url | https://elifesciences.org/articles/88828 |
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