NudC L279P Mutation Destabilizes Filamin A by Inhibiting the Hsp90 Chaperoning Pathway and Suppresses Cell Migration
Filamin A, the first discovered non-muscle actin filament cross-linking protein, plays a crucial role in regulating cell migration that participates in diverse cellular and developmental processes. However, the regulatory mechanism of filamin A stability remains unclear. Here, we find that nuclear d...
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| Format: | Article |
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Frontiers Media S.A.
2021-06-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2021.671233/full |
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| author | Min Liu Zhangqi Xu Cheng Zhang Chunxia Yang Jiaxing Feng Yiqing Lu Wen Zhang Wenwen Chen Xiaoyang Xu Xiaoxia Sun Mingyang Yang Wei Liu Tianhua Zhou Tianhua Zhou Tianhua Zhou Tianhua Zhou Yuehong Yang |
| author_facet | Min Liu Zhangqi Xu Cheng Zhang Chunxia Yang Jiaxing Feng Yiqing Lu Wen Zhang Wenwen Chen Xiaoyang Xu Xiaoxia Sun Mingyang Yang Wei Liu Tianhua Zhou Tianhua Zhou Tianhua Zhou Tianhua Zhou Yuehong Yang |
| author_sort | Min Liu |
| collection | DOAJ |
| description | Filamin A, the first discovered non-muscle actin filament cross-linking protein, plays a crucial role in regulating cell migration that participates in diverse cellular and developmental processes. However, the regulatory mechanism of filamin A stability remains unclear. Here, we find that nuclear distribution gene C (NudC), a cochaperone of heat shock protein 90 (Hsp90), is required to stabilize filamin A in mammalian cells. Immunoprecipitation-mass spectrometry and western blotting analyses reveal that NudC interacts with filamin A. Overexpression of human NudC-L279P (an evolutionarily conserved mutation in NudC that impairs its chaperone activity) not only decreases the protein level of filamin A but also results in actin disorganization and the suppression of cell migration. Ectopic expression of filamin A is able to reverse these defects induced by the overexpression of NudC-L279P. Furthermore, Hsp90 forms a complex with filamin A. The inhibition of Hsp90 ATPase activity by either geldanamycin or radicicol decreases the protein stability of filamin A. In addition, ectopic expression of Hsp90 efficiently restores NudC-L279P overexpression-induced protein stability and functional defects of filamin A. Taken together, these data suggest NudC L279P mutation destabilizes filamin A by inhibiting the Hsp90 chaperoning pathway and suppresses cell migration. |
| first_indexed | 2024-04-09T21:17:15Z |
| format | Article |
| id | doaj.art-4a26e376634048b684125bec02e5da52 |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-04-09T21:17:15Z |
| publishDate | 2021-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-4a26e376634048b684125bec02e5da522023-03-28T07:23:44ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2021-06-01910.3389/fcell.2021.671233671233NudC L279P Mutation Destabilizes Filamin A by Inhibiting the Hsp90 Chaperoning Pathway and Suppresses Cell MigrationMin Liu0Zhangqi Xu1Cheng Zhang2Chunxia Yang3Jiaxing Feng4Yiqing Lu5Wen Zhang6Wenwen Chen7Xiaoyang Xu8Xiaoxia Sun9Mingyang Yang10Wei Liu11Tianhua Zhou12Tianhua Zhou13Tianhua Zhou14Tianhua Zhou15Yuehong Yang16Department of Cell Biology, and Institute of Gastroenterology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Cell Biology, and Institute of Gastroenterology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Cell Biology, and Institute of Gastroenterology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Cell Biology, and Institute of Gastroenterology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Cell Biology, and Institute of Gastroenterology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Cell Biology, and Institute of Gastroenterology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Cell Biology, and Institute of Gastroenterology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Cell Biology, and Institute of Gastroenterology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Cell Biology, and Institute of Gastroenterology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Cell Biology, and Institute of Gastroenterology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Cell Biology, and Institute of Gastroenterology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Cell Biology, and Institute of Gastroenterology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaDepartment of Cell Biology, and Institute of Gastroenterology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaThe Cancer Center of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaCollaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, ChinaDepartment of Molecular Genetics, University of Toronto, Toronto, ON, CanadaDepartment of Cell Biology, and Institute of Gastroenterology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, ChinaFilamin A, the first discovered non-muscle actin filament cross-linking protein, plays a crucial role in regulating cell migration that participates in diverse cellular and developmental processes. However, the regulatory mechanism of filamin A stability remains unclear. Here, we find that nuclear distribution gene C (NudC), a cochaperone of heat shock protein 90 (Hsp90), is required to stabilize filamin A in mammalian cells. Immunoprecipitation-mass spectrometry and western blotting analyses reveal that NudC interacts with filamin A. Overexpression of human NudC-L279P (an evolutionarily conserved mutation in NudC that impairs its chaperone activity) not only decreases the protein level of filamin A but also results in actin disorganization and the suppression of cell migration. Ectopic expression of filamin A is able to reverse these defects induced by the overexpression of NudC-L279P. Furthermore, Hsp90 forms a complex with filamin A. The inhibition of Hsp90 ATPase activity by either geldanamycin or radicicol decreases the protein stability of filamin A. In addition, ectopic expression of Hsp90 efficiently restores NudC-L279P overexpression-induced protein stability and functional defects of filamin A. Taken together, these data suggest NudC L279P mutation destabilizes filamin A by inhibiting the Hsp90 chaperoning pathway and suppresses cell migration.https://www.frontiersin.org/articles/10.3389/fcell.2021.671233/fullcell migrationfilamin AHsp90NudC-L279Pprotein stability |
| spellingShingle | Min Liu Zhangqi Xu Cheng Zhang Chunxia Yang Jiaxing Feng Yiqing Lu Wen Zhang Wenwen Chen Xiaoyang Xu Xiaoxia Sun Mingyang Yang Wei Liu Tianhua Zhou Tianhua Zhou Tianhua Zhou Tianhua Zhou Yuehong Yang NudC L279P Mutation Destabilizes Filamin A by Inhibiting the Hsp90 Chaperoning Pathway and Suppresses Cell Migration Frontiers in Cell and Developmental Biology cell migration filamin A Hsp90 NudC-L279P protein stability |
| title | NudC L279P Mutation Destabilizes Filamin A by Inhibiting the Hsp90 Chaperoning Pathway and Suppresses Cell Migration |
| title_full | NudC L279P Mutation Destabilizes Filamin A by Inhibiting the Hsp90 Chaperoning Pathway and Suppresses Cell Migration |
| title_fullStr | NudC L279P Mutation Destabilizes Filamin A by Inhibiting the Hsp90 Chaperoning Pathway and Suppresses Cell Migration |
| title_full_unstemmed | NudC L279P Mutation Destabilizes Filamin A by Inhibiting the Hsp90 Chaperoning Pathway and Suppresses Cell Migration |
| title_short | NudC L279P Mutation Destabilizes Filamin A by Inhibiting the Hsp90 Chaperoning Pathway and Suppresses Cell Migration |
| title_sort | nudc l279p mutation destabilizes filamin a by inhibiting the hsp90 chaperoning pathway and suppresses cell migration |
| topic | cell migration filamin A Hsp90 NudC-L279P protein stability |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2021.671233/full |
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