Interaction between DLC-1 and SAO-1 facilitates CED-4 translocation during apoptosis in the Caenorhabditis elegans germline
Abstract Apoptosis is one of the major forms of programmed cell death, and it serves vital biological functions in multicellular animal and plant cells. The core mechanism of apoptosis is highly conserved in metazoans, where the translocation of CED-4/Apaf-1 from mitochondria to the nuclear membrane...
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Nature Publishing Group
2022-11-01
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Series: | Cell Death Discovery |
Online Access: | https://doi.org/10.1038/s41420-022-01233-9 |
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author | Dandan Zhang Haibin Yang Ling Jiang Chan Zhao Mengjun Wang Boyi Hu Cong Yu Zhiyi Wei Yu Chung Tse |
author_facet | Dandan Zhang Haibin Yang Ling Jiang Chan Zhao Mengjun Wang Boyi Hu Cong Yu Zhiyi Wei Yu Chung Tse |
author_sort | Dandan Zhang |
collection | DOAJ |
description | Abstract Apoptosis is one of the major forms of programmed cell death, and it serves vital biological functions in multicellular animal and plant cells. The core mechanism of apoptosis is highly conserved in metazoans, where the translocation of CED-4/Apaf-1 from mitochondria to the nuclear membrane is required to initiate and execute apoptosis. However, the underlying molecular mechanisms of this translocation are poorly understood. In this study, we showed that SAO-1 binds DLC-1 and prevents its degradation to promote apoptosis in C. elegans germ cells. We demonstrated that SAO-1 and DLC-1 regulate CED-4/Apaf-1 nuclear membrane accumulation during apoptosis. Isothermal titration calorimetry-based assay and high-resolution crystal structure analysis further revealed that SAO-1 interacted with DLC-1 to form a 2:4 complex: each of the two β-sheets in the SAO-1 peptide interacted with two DLC-1 dimers. Point mutations at the SAO-1-DLC-1 binding interface significantly inhibited apoptotic corpse formation and CED-4 nuclear membrane accumulation within C. elegans germ cells. In conclusion, our study provides a new perspective on the regulation of CED-4-mediated apoptosis. |
first_indexed | 2024-04-12T11:23:54Z |
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id | doaj.art-035873588c184e379c870949e3596ba3 |
institution | Directory Open Access Journal |
issn | 2058-7716 |
language | English |
last_indexed | 2024-04-12T11:23:54Z |
publishDate | 2022-11-01 |
publisher | Nature Publishing Group |
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series | Cell Death Discovery |
spelling | doaj.art-035873588c184e379c870949e3596ba32022-12-22T03:35:16ZengNature Publishing GroupCell Death Discovery2058-77162022-11-018111110.1038/s41420-022-01233-9Interaction between DLC-1 and SAO-1 facilitates CED-4 translocation during apoptosis in the Caenorhabditis elegans germlineDandan Zhang0Haibin Yang1Ling Jiang2Chan Zhao3Mengjun Wang4Boyi Hu5Cong Yu6Zhiyi Wei7Yu Chung Tse8School of Life Science and Technology, Harbin Institute of TechnologySchool of Life Sciences, Department of Biology, Southern University of Science and TechnologySchool of Life Sciences, Department of Biology, Southern University of Science and TechnologySchool of Life Sciences, Department of Biology, Southern University of Science and TechnologySchool of Life Sciences, Department of Biology, Southern University of Science and TechnologySchool of Life Sciences, Department of Biology, Southern University of Science and TechnologySchool of Life Sciences, Department of Biology, Southern University of Science and TechnologySchool of Life Sciences, Department of Biology, Southern University of Science and TechnologyGuangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research, Southern University of Science and TechnologyAbstract Apoptosis is one of the major forms of programmed cell death, and it serves vital biological functions in multicellular animal and plant cells. The core mechanism of apoptosis is highly conserved in metazoans, where the translocation of CED-4/Apaf-1 from mitochondria to the nuclear membrane is required to initiate and execute apoptosis. However, the underlying molecular mechanisms of this translocation are poorly understood. In this study, we showed that SAO-1 binds DLC-1 and prevents its degradation to promote apoptosis in C. elegans germ cells. We demonstrated that SAO-1 and DLC-1 regulate CED-4/Apaf-1 nuclear membrane accumulation during apoptosis. Isothermal titration calorimetry-based assay and high-resolution crystal structure analysis further revealed that SAO-1 interacted with DLC-1 to form a 2:4 complex: each of the two β-sheets in the SAO-1 peptide interacted with two DLC-1 dimers. Point mutations at the SAO-1-DLC-1 binding interface significantly inhibited apoptotic corpse formation and CED-4 nuclear membrane accumulation within C. elegans germ cells. In conclusion, our study provides a new perspective on the regulation of CED-4-mediated apoptosis.https://doi.org/10.1038/s41420-022-01233-9 |
spellingShingle | Dandan Zhang Haibin Yang Ling Jiang Chan Zhao Mengjun Wang Boyi Hu Cong Yu Zhiyi Wei Yu Chung Tse Interaction between DLC-1 and SAO-1 facilitates CED-4 translocation during apoptosis in the Caenorhabditis elegans germline Cell Death Discovery |
title | Interaction between DLC-1 and SAO-1 facilitates CED-4 translocation during apoptosis in the Caenorhabditis elegans germline |
title_full | Interaction between DLC-1 and SAO-1 facilitates CED-4 translocation during apoptosis in the Caenorhabditis elegans germline |
title_fullStr | Interaction between DLC-1 and SAO-1 facilitates CED-4 translocation during apoptosis in the Caenorhabditis elegans germline |
title_full_unstemmed | Interaction between DLC-1 and SAO-1 facilitates CED-4 translocation during apoptosis in the Caenorhabditis elegans germline |
title_short | Interaction between DLC-1 and SAO-1 facilitates CED-4 translocation during apoptosis in the Caenorhabditis elegans germline |
title_sort | interaction between dlc 1 and sao 1 facilitates ced 4 translocation during apoptosis in the caenorhabditis elegans germline |
url | https://doi.org/10.1038/s41420-022-01233-9 |
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