NLRP14 Safeguards Calcium Homeostasis via Regulating the K27 Ubiquitination of Nclx in Oocyte‐to‐Embryo Transition
Abstract Sperm‐induced Ca2+ rise is critical for driving oocyte activation and subsequent embryonic development, but little is known about how lasting Ca2+ oscillations are regulated. Here it is shown that NLRP14, a maternal effect factor, is essential for keeping Ca2+ oscillations and early embryon...
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2023-09-01
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| Series: | Advanced Science |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/advs.202301940 |
| _version_ | 1797673981541613568 |
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| author | Tie‐Gang Meng Jia‐Ni Guo Liu Zhu Yike Yin Feng Wang Zhi‐Ming Han Lei Lei Xue‐Shan Ma Yue Xue Wei Yue Xiao‐Qing Nie Zheng‐Hui Zhao Hong‐Yong Zhang Si‐Min Sun Ying‐Chun Ouyang Yi Hou Heide Schatten Zhenyu Ju Xiang‐Hong Ou Zhen‐Bo Wang Catherine C. L. Wong Zhonghan Li Qing‐Yuan Sun |
| author_facet | Tie‐Gang Meng Jia‐Ni Guo Liu Zhu Yike Yin Feng Wang Zhi‐Ming Han Lei Lei Xue‐Shan Ma Yue Xue Wei Yue Xiao‐Qing Nie Zheng‐Hui Zhao Hong‐Yong Zhang Si‐Min Sun Ying‐Chun Ouyang Yi Hou Heide Schatten Zhenyu Ju Xiang‐Hong Ou Zhen‐Bo Wang Catherine C. L. Wong Zhonghan Li Qing‐Yuan Sun |
| author_sort | Tie‐Gang Meng |
| collection | DOAJ |
| description | Abstract Sperm‐induced Ca2+ rise is critical for driving oocyte activation and subsequent embryonic development, but little is known about how lasting Ca2+ oscillations are regulated. Here it is shown that NLRP14, a maternal effect factor, is essential for keeping Ca2+ oscillations and early embryonic development. Few embryos lacking maternal NLRP14 can develop beyond the 2‐cell stage. The impaired developmental potential of Nlrp14‐deficient oocytes is mainly caused by disrupted cytoplasmic function and calcium homeostasis due to altered mitochondrial distribution, morphology, and activity since the calcium oscillations and development of Nlrp14‐deficient oocytes can be rescued by substitution of whole cytoplasm by spindle transfer. Proteomics analysis reveal that cytoplasmic UHRF1 (ubiquitin‐like, containing PHD and RING finger domains 1) is significantly decreased in Nlrp14‐deficient oocytes, and Uhrf1‐deficient oocytes also show disrupted calcium homeostasis and developmental arrest. Strikingly, it is found that the mitochondrial Na+/Ca2+ exchanger (NCLX) encoded by Slc8b1 is significantly decreased in the Nlrp14mNull oocyte. Mechanistically, NLRP14 interacts with the NCLX intrinsically disordered regions (IDRs) domain and maintain its stability by regulating the K27‐linked ubiquitination. Thus, the study reveals NLRP14 as a crucial player in calcium homeostasis that is important for early embryonic development. |
| first_indexed | 2024-03-11T21:52:26Z |
| format | Article |
| id | doaj.art-47580a10099a4e6e94ff73db2cf2e674 |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-03-11T21:52:26Z |
| publishDate | 2023-09-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj.art-47580a10099a4e6e94ff73db2cf2e6742023-09-26T07:39:32ZengWileyAdvanced Science2198-38442023-09-011027n/an/a10.1002/advs.202301940NLRP14 Safeguards Calcium Homeostasis via Regulating the K27 Ubiquitination of Nclx in Oocyte‐to‐Embryo TransitionTie‐Gang Meng0Jia‐Ni Guo1Liu Zhu2Yike Yin3Feng Wang4Zhi‐Ming Han5Lei Lei6Xue‐Shan Ma7Yue Xue8Wei Yue9Xiao‐Qing Nie10Zheng‐Hui Zhao11Hong‐Yong Zhang12Si‐Min Sun13Ying‐Chun Ouyang14Yi Hou15Heide Schatten16Zhenyu Ju17Xiang‐Hong Ou18Zhen‐Bo Wang19Catherine C. L. Wong20Zhonghan Li21Qing‐Yuan Sun22Fertility Preservation Lab Guangdong‐Hong Kong Metabolism and Reproduction Joint Laboratory Reproductive Medicine Center Guangdong Second Provincial General Hospital Guangzhou 510317 P. R. ChinaState Key Laboratory of Stem Cell and Reproductive Biology Institute of Zoology Chinese Academy of Sciences Beijing 100101 P. R. ChinaSchool of Basic Medical Sciences Peking University Health Science Center Beijing 100191 P. R. ChinaCenter for Growth Metabolism & Aging Key Laboratory of Bio‐Resource and Eco‐Environment of Ministry of Education College of Life Sciences Sichuan University Chengdu 610017 P. R. ChinaState Key Laboratory of Stem Cell and Reproductive Biology Institute of Zoology Chinese Academy of Sciences Beijing 100101 P. R. ChinaState Key Laboratory of Stem Cell and Reproductive Biology Institute of Zoology Chinese Academy of Sciences Beijing 100101 P. R. ChinaDepartment of Histology and Embryology Harbin Medical University Harbin 150088 P. R. ChinaState Key Laboratory of Stem Cell and Reproductive Biology Institute of Zoology Chinese Academy of Sciences Beijing 100101 P. R. ChinaState Key Laboratory of Stem Cell and Reproductive Biology Institute of Zoology Chinese Academy of Sciences Beijing 100101 P. R. ChinaState Key Laboratory of Stem Cell and Reproductive Biology Institute of Zoology Chinese Academy of Sciences Beijing 100101 P. R. ChinaState Key Laboratory of Stem Cell and Reproductive Biology Institute of Zoology Chinese Academy of Sciences Beijing 100101 P. R. ChinaFertility Preservation Lab Guangdong‐Hong Kong Metabolism and Reproduction Joint Laboratory Reproductive Medicine Center Guangdong Second Provincial General Hospital Guangzhou 510317 P. R. ChinaState Key Laboratory of Stem Cell and Reproductive Biology Institute of Zoology Chinese Academy of Sciences Beijing 100101 P. R. ChinaState Key Laboratory of Stem Cell and Reproductive Biology Institute of Zoology Chinese Academy of Sciences Beijing 100101 P. R. ChinaState Key Laboratory of Stem Cell and Reproductive Biology Institute of Zoology Chinese Academy of Sciences Beijing 100101 P. R. ChinaState Key Laboratory of Stem Cell and Reproductive Biology Institute of Zoology Chinese Academy of Sciences Beijing 100101 P. R. ChinaDepartment of Veterinary Pathobiology University of Missouri Columbia MO 65211 USAKey Laboratory of Regenerative Medicine of Ministry of Education Institute of Aging and Regenerative Medicine Jinan University Guangzhou Guangdong 510632 P. R. ChinaFertility Preservation Lab Guangdong‐Hong Kong Metabolism and Reproduction Joint Laboratory Reproductive Medicine Center Guangdong Second Provincial General Hospital Guangzhou 510317 P. R. ChinaState Key Laboratory of Stem Cell and Reproductive Biology Institute of Zoology Chinese Academy of Sciences Beijing 100101 P. R. ChinaDepartment of Medical Research Center State Key Laboratory of Complex Severe and Rare Diseases Peking Union Medical College Hospital Chinese Academy of Medical Science & Peking Union Medical College Beijing 100730 P. R. ChinaCenter for Growth Metabolism & Aging Key Laboratory of Bio‐Resource and Eco‐Environment of Ministry of Education College of Life Sciences Sichuan University Chengdu 610017 P. R. ChinaFertility Preservation Lab Guangdong‐Hong Kong Metabolism and Reproduction Joint Laboratory Reproductive Medicine Center Guangdong Second Provincial General Hospital Guangzhou 510317 P. R. ChinaAbstract Sperm‐induced Ca2+ rise is critical for driving oocyte activation and subsequent embryonic development, but little is known about how lasting Ca2+ oscillations are regulated. Here it is shown that NLRP14, a maternal effect factor, is essential for keeping Ca2+ oscillations and early embryonic development. Few embryos lacking maternal NLRP14 can develop beyond the 2‐cell stage. The impaired developmental potential of Nlrp14‐deficient oocytes is mainly caused by disrupted cytoplasmic function and calcium homeostasis due to altered mitochondrial distribution, morphology, and activity since the calcium oscillations and development of Nlrp14‐deficient oocytes can be rescued by substitution of whole cytoplasm by spindle transfer. Proteomics analysis reveal that cytoplasmic UHRF1 (ubiquitin‐like, containing PHD and RING finger domains 1) is significantly decreased in Nlrp14‐deficient oocytes, and Uhrf1‐deficient oocytes also show disrupted calcium homeostasis and developmental arrest. Strikingly, it is found that the mitochondrial Na+/Ca2+ exchanger (NCLX) encoded by Slc8b1 is significantly decreased in the Nlrp14mNull oocyte. Mechanistically, NLRP14 interacts with the NCLX intrinsically disordered regions (IDRs) domain and maintain its stability by regulating the K27‐linked ubiquitination. Thus, the study reveals NLRP14 as a crucial player in calcium homeostasis that is important for early embryonic development.https://doi.org/10.1002/advs.202301940adenosine triphosphate (ATP)calcium homeostasisearly embryonic developmentmaternal effect genesmitochondriaNCLX |
| spellingShingle | Tie‐Gang Meng Jia‐Ni Guo Liu Zhu Yike Yin Feng Wang Zhi‐Ming Han Lei Lei Xue‐Shan Ma Yue Xue Wei Yue Xiao‐Qing Nie Zheng‐Hui Zhao Hong‐Yong Zhang Si‐Min Sun Ying‐Chun Ouyang Yi Hou Heide Schatten Zhenyu Ju Xiang‐Hong Ou Zhen‐Bo Wang Catherine C. L. Wong Zhonghan Li Qing‐Yuan Sun NLRP14 Safeguards Calcium Homeostasis via Regulating the K27 Ubiquitination of Nclx in Oocyte‐to‐Embryo Transition Advanced Science adenosine triphosphate (ATP) calcium homeostasis early embryonic development maternal effect genes mitochondria NCLX |
| title | NLRP14 Safeguards Calcium Homeostasis via Regulating the K27 Ubiquitination of Nclx in Oocyte‐to‐Embryo Transition |
| title_full | NLRP14 Safeguards Calcium Homeostasis via Regulating the K27 Ubiquitination of Nclx in Oocyte‐to‐Embryo Transition |
| title_fullStr | NLRP14 Safeguards Calcium Homeostasis via Regulating the K27 Ubiquitination of Nclx in Oocyte‐to‐Embryo Transition |
| title_full_unstemmed | NLRP14 Safeguards Calcium Homeostasis via Regulating the K27 Ubiquitination of Nclx in Oocyte‐to‐Embryo Transition |
| title_short | NLRP14 Safeguards Calcium Homeostasis via Regulating the K27 Ubiquitination of Nclx in Oocyte‐to‐Embryo Transition |
| title_sort | nlrp14 safeguards calcium homeostasis via regulating the k27 ubiquitination of nclx in oocyte to embryo transition |
| topic | adenosine triphosphate (ATP) calcium homeostasis early embryonic development maternal effect genes mitochondria NCLX |
| url | https://doi.org/10.1002/advs.202301940 |
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