DHHC2 regulates fear memory formation, LTP, and AKAP150 signaling in the hippocampus
Summary: Palmitoyl acyltransferases (PATs) have been suggested to be involved in learning and memory. However, the underlying mechanisms have not yet been fully elucidated. Here, we found that the activity of DHHC2 was upregulated in the hippocampus after fear conditioning, and DHHC2 knockdown impai...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-09-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004223016383 |
| _version_ | 1797740809788850176 |
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| author | Meng-Die Li Lu Wang Yu-Qi Zheng Dan-Hong Huang Zhi-Xuan Xia Jian-Min Liu Dan Tian Hui OuYang Zi-Hao Wang Zhen Huang Xiao-Shan Lin Xiao-Qian Zhu Si-Ying Wang Wei-Kai Chen Shao-Wei Yang Yue-Ling Zhao Jia-An Liu Zu-Cheng Shen |
| author_facet | Meng-Die Li Lu Wang Yu-Qi Zheng Dan-Hong Huang Zhi-Xuan Xia Jian-Min Liu Dan Tian Hui OuYang Zi-Hao Wang Zhen Huang Xiao-Shan Lin Xiao-Qian Zhu Si-Ying Wang Wei-Kai Chen Shao-Wei Yang Yue-Ling Zhao Jia-An Liu Zu-Cheng Shen |
| author_sort | Meng-Die Li |
| collection | DOAJ |
| description | Summary: Palmitoyl acyltransferases (PATs) have been suggested to be involved in learning and memory. However, the underlying mechanisms have not yet been fully elucidated. Here, we found that the activity of DHHC2 was upregulated in the hippocampus after fear conditioning, and DHHC2 knockdown impaired fear induced memory and long-term potentiation (LTP). Additionally, the activity of DHHC2 and its synaptic expression were increased after high frequency stimulation (HFS) or glycine treatment. Importantly, fear learning selectively augmented the palmitoylation level of AKAP150, not PSD-95, and this effect was abolished by DHHC2 knockdown. Furthermore, 2-bromopalmitic acid (2-BP), a palmitoylation inhibitor, attenuated the increased palmitoylation level of AKAP150 and the interaction between AKAP150 and PSD-95 induced by HFS. Lastly, DHHC2 knockdown reduced the phosphorylation level of GluA1 at Ser845, and also induced an impairment of LTP in the hippocampus. Our results suggest that DHHC2 plays a critical role in regulating fear memory via AKAP150 signaling. |
| first_indexed | 2024-03-12T14:18:48Z |
| format | Article |
| id | doaj.art-b9a49af21c67450d8224e6de117c7de0 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-03-12T14:18:48Z |
| publishDate | 2023-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-b9a49af21c67450d8224e6de117c7de02023-08-20T04:38:27ZengElsevieriScience2589-00422023-09-01269107561DHHC2 regulates fear memory formation, LTP, and AKAP150 signaling in the hippocampusMeng-Die Li0Lu Wang1Yu-Qi Zheng2Dan-Hong Huang3Zhi-Xuan Xia4Jian-Min Liu5Dan Tian6Hui OuYang7Zi-Hao Wang8Zhen Huang9Xiao-Shan Lin10Xiao-Qian Zhu11Si-Ying Wang12Wei-Kai Chen13Shao-Wei Yang14Yue-Ling Zhao15Jia-An Liu16Zu-Cheng Shen17Department of Pharmacology, School of Pharmacy, Fujian Medical University, Fuzhou 350122, ChinaDepartment of Nephrology, Fuzhou Children’s Hospital of Fujian Province, Affiliated Hospital of Fujian Medical University, Fuzhou 350001, ChinaDepartment of Pharmacology, School of Pharmacy, Fujian Medical University, Fuzhou 350122, ChinaDepartment of Pharmacology, School of Pharmacy, Fujian Medical University, Fuzhou 350122, ChinaDepartment of Pharmacology, School of Basic Medicine and Life Science, Hainan Medical University, Haikou 571199, ChinaDepartment of Pharmacy, Wuhan No. 1 Hospital, Wuhan 430000, ChinaDepartment of Pharmacology, School of Pharmacy, Fujian Medical University, Fuzhou 350122, ChinaDepartment of Pharmacology, School of Pharmacy, Fujian Medical University, Fuzhou 350122, ChinaGuangdong Provincial Key Laboratory of Brain Function and Disease, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, ChinaDepartment of Pharmacology, School of Pharmacy, Fujian Medical University, Fuzhou 350122, ChinaDepartment of Pharmacology, School of Pharmacy, Fujian Medical University, Fuzhou 350122, ChinaDepartment of Pharmacology, School of Pharmacy, Fujian Medical University, Fuzhou 350122, ChinaDepartment of Pharmacology, School of Pharmacy, Fujian Medical University, Fuzhou 350122, ChinaDepartment of Pharmacology, School of Pharmacy, Fujian Medical University, Fuzhou 350122, ChinaDepartment of Pharmacology, School of Pharmacy, Fujian Medical University, Fuzhou 350122, ChinaDepartment of Pharmacology, School of Pharmacy, Fujian Medical University, Fuzhou 350122, ChinaDepartment of Medicinal Chemistry, School of Pharmacy, Fujian Medical University, Fuzhou 350122, China; Corresponding authorDepartment of Pharmacology, School of Pharmacy, Fujian Medical University, Fuzhou 350122, China; Corresponding authorSummary: Palmitoyl acyltransferases (PATs) have been suggested to be involved in learning and memory. However, the underlying mechanisms have not yet been fully elucidated. Here, we found that the activity of DHHC2 was upregulated in the hippocampus after fear conditioning, and DHHC2 knockdown impaired fear induced memory and long-term potentiation (LTP). Additionally, the activity of DHHC2 and its synaptic expression were increased after high frequency stimulation (HFS) or glycine treatment. Importantly, fear learning selectively augmented the palmitoylation level of AKAP150, not PSD-95, and this effect was abolished by DHHC2 knockdown. Furthermore, 2-bromopalmitic acid (2-BP), a palmitoylation inhibitor, attenuated the increased palmitoylation level of AKAP150 and the interaction between AKAP150 and PSD-95 induced by HFS. Lastly, DHHC2 knockdown reduced the phosphorylation level of GluA1 at Ser845, and also induced an impairment of LTP in the hippocampus. Our results suggest that DHHC2 plays a critical role in regulating fear memory via AKAP150 signaling.http://www.sciencedirect.com/science/article/pii/S2589004223016383BiochemistryMolecular biologyNeuroscience |
| spellingShingle | Meng-Die Li Lu Wang Yu-Qi Zheng Dan-Hong Huang Zhi-Xuan Xia Jian-Min Liu Dan Tian Hui OuYang Zi-Hao Wang Zhen Huang Xiao-Shan Lin Xiao-Qian Zhu Si-Ying Wang Wei-Kai Chen Shao-Wei Yang Yue-Ling Zhao Jia-An Liu Zu-Cheng Shen DHHC2 regulates fear memory formation, LTP, and AKAP150 signaling in the hippocampus iScience Biochemistry Molecular biology Neuroscience |
| title | DHHC2 regulates fear memory formation, LTP, and AKAP150 signaling in the hippocampus |
| title_full | DHHC2 regulates fear memory formation, LTP, and AKAP150 signaling in the hippocampus |
| title_fullStr | DHHC2 regulates fear memory formation, LTP, and AKAP150 signaling in the hippocampus |
| title_full_unstemmed | DHHC2 regulates fear memory formation, LTP, and AKAP150 signaling in the hippocampus |
| title_short | DHHC2 regulates fear memory formation, LTP, and AKAP150 signaling in the hippocampus |
| title_sort | dhhc2 regulates fear memory formation ltp and akap150 signaling in the hippocampus |
| topic | Biochemistry Molecular biology Neuroscience |
| url | http://www.sciencedirect.com/science/article/pii/S2589004223016383 |
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