Type III intermediate filaments as targets and effectors of electrophiles and oxidants
Intermediate filaments (IFs) play key roles in cell mechanics, signaling and homeostasis. Their assembly and dynamics are finely regulated by posttranslational modifications. The type III IFs, vimentin, desmin, peripherin and glial fibrillary acidic protein (GFAP), are targets for diverse modificati...
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| Format: | Article |
| Language: | English |
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Elsevier
2020-09-01
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| Series: | Redox Biology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213231720302202 |
| _version_ | 1819018743802494976 |
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| author | Álvaro Viedma-Poyatos María A. Pajares Dolores Pérez-Sala |
| author_facet | Álvaro Viedma-Poyatos María A. Pajares Dolores Pérez-Sala |
| author_sort | Álvaro Viedma-Poyatos |
| collection | DOAJ |
| description | Intermediate filaments (IFs) play key roles in cell mechanics, signaling and homeostasis. Their assembly and dynamics are finely regulated by posttranslational modifications. The type III IFs, vimentin, desmin, peripherin and glial fibrillary acidic protein (GFAP), are targets for diverse modifications by oxidants and electrophiles, for which their conserved cysteine residue emerges as a hot spot. Pathophysiological examples of these modifications include lipoxidation in cell senescence and rheumatoid arthritis, disulfide formation in cataracts and nitrosation in endothelial shear stress, although some oxidative modifications can also be detected under basal conditions. We previously proposed that cysteine residues of vimentin and GFAP act as sensors for oxidative and electrophilic stress, and as hinges influencing filament assembly. Accumulating evidence indicates that the structurally diverse cysteine modifications, either per se or in combination with other posttranslational modifications, elicit specific functional outcomes inducing distinct assemblies or network rearrangements, including filament stabilization, bundling or fragmentation. Cysteine-deficient mutants are protected from these alterations but show compromised cellular performance in network assembly and expansion, organelle positioning and aggresome formation, revealing the importance of this residue. Therefore, the high susceptibility to modification of the conserved cysteine of type III IFs and its cornerstone position in filament architecture sustains their role in redox sensing and integration of cellular responses. This has deep pathophysiological implications and supports the potential of this residue as a drug target. |
| first_indexed | 2024-12-21T03:24:17Z |
| format | Article |
| id | doaj.art-a8a5aed504024cc2b376c40001236921 |
| institution | Directory Open Access Journal |
| issn | 2213-2317 |
| language | English |
| last_indexed | 2024-12-21T03:24:17Z |
| publishDate | 2020-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Redox Biology |
| spelling | doaj.art-a8a5aed504024cc2b376c400012369212022-12-21T19:17:39ZengElsevierRedox Biology2213-23172020-09-0136101582Type III intermediate filaments as targets and effectors of electrophiles and oxidantsÁlvaro Viedma-Poyatos0María A. Pajares1Dolores Pérez-Sala2Department of Chemical and Structural Biology, Centro de Investigaciones Biológicas Margarita Salas (CSIC), Ramiro de Maeztu, 9, 28040, Madrid, SpainDepartment of Chemical and Structural Biology, Centro de Investigaciones Biológicas Margarita Salas (CSIC), Ramiro de Maeztu, 9, 28040, Madrid, SpainCorresponding author. Department of Structural and Chemical Biology, Centro de Investigaciones Biológicas Margarita Salas, Consejo Superior de Investigaciones Científicas (C.S.I.C.), Ramiro de Maeztu, 9, 28040, Madrid, Spain.; Department of Chemical and Structural Biology, Centro de Investigaciones Biológicas Margarita Salas (CSIC), Ramiro de Maeztu, 9, 28040, Madrid, SpainIntermediate filaments (IFs) play key roles in cell mechanics, signaling and homeostasis. Their assembly and dynamics are finely regulated by posttranslational modifications. The type III IFs, vimentin, desmin, peripherin and glial fibrillary acidic protein (GFAP), are targets for diverse modifications by oxidants and electrophiles, for which their conserved cysteine residue emerges as a hot spot. Pathophysiological examples of these modifications include lipoxidation in cell senescence and rheumatoid arthritis, disulfide formation in cataracts and nitrosation in endothelial shear stress, although some oxidative modifications can also be detected under basal conditions. We previously proposed that cysteine residues of vimentin and GFAP act as sensors for oxidative and electrophilic stress, and as hinges influencing filament assembly. Accumulating evidence indicates that the structurally diverse cysteine modifications, either per se or in combination with other posttranslational modifications, elicit specific functional outcomes inducing distinct assemblies or network rearrangements, including filament stabilization, bundling or fragmentation. Cysteine-deficient mutants are protected from these alterations but show compromised cellular performance in network assembly and expansion, organelle positioning and aggresome formation, revealing the importance of this residue. Therefore, the high susceptibility to modification of the conserved cysteine of type III IFs and its cornerstone position in filament architecture sustains their role in redox sensing and integration of cellular responses. This has deep pathophysiological implications and supports the potential of this residue as a drug target.http://www.sciencedirect.com/science/article/pii/S2213231720302202VimentinGFAPDesminRedox sensingCysteine oxidative modificationsLipoxidation |
| spellingShingle | Álvaro Viedma-Poyatos María A. Pajares Dolores Pérez-Sala Type III intermediate filaments as targets and effectors of electrophiles and oxidants Redox Biology Vimentin GFAP Desmin Redox sensing Cysteine oxidative modifications Lipoxidation |
| title | Type III intermediate filaments as targets and effectors of electrophiles and oxidants |
| title_full | Type III intermediate filaments as targets and effectors of electrophiles and oxidants |
| title_fullStr | Type III intermediate filaments as targets and effectors of electrophiles and oxidants |
| title_full_unstemmed | Type III intermediate filaments as targets and effectors of electrophiles and oxidants |
| title_short | Type III intermediate filaments as targets and effectors of electrophiles and oxidants |
| title_sort | type iii intermediate filaments as targets and effectors of electrophiles and oxidants |
| topic | Vimentin GFAP Desmin Redox sensing Cysteine oxidative modifications Lipoxidation |
| url | http://www.sciencedirect.com/science/article/pii/S2213231720302202 |
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