Cd99l2 regulates excitatory synapse development and restrains immediate-early gene activation
Summary: Cd99 molecule-like 2 (Cd99l2) is a type I transmembrane protein that plays a role in the transmigration of leukocytes across vascular endothelial cells. Despite its high expression in the brain, the role of Cd99l2 remains elusive. We find that Cd99l2 is expressed primarily in neurons and po...
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| Language: | English |
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Elsevier
2025-01-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124724015067 |
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| author | Minji Kang Sang Ho Yoon Minkyung Kang Seung Pyo Park Woo Seok Song Jungho Kim Seungha Lee Da-ha Park Jae-man Song Beomsue Kim Kyung Hee Park Eun-Hye Joe Hyun Goo Woo Seong Hoe Park Bong-Kiun Kaang Dohyun Han Yong-Seok Lee Myoung-Hwan Kim Young Ho Suh |
| author_facet | Minji Kang Sang Ho Yoon Minkyung Kang Seung Pyo Park Woo Seok Song Jungho Kim Seungha Lee Da-ha Park Jae-man Song Beomsue Kim Kyung Hee Park Eun-Hye Joe Hyun Goo Woo Seong Hoe Park Bong-Kiun Kaang Dohyun Han Yong-Seok Lee Myoung-Hwan Kim Young Ho Suh |
| author_sort | Minji Kang |
| collection | DOAJ |
| description | Summary: Cd99 molecule-like 2 (Cd99l2) is a type I transmembrane protein that plays a role in the transmigration of leukocytes across vascular endothelial cells. Despite its high expression in the brain, the role of Cd99l2 remains elusive. We find that Cd99l2 is expressed primarily in neurons and positively regulates neurite outgrowth and the development of excitatory synapses. We demonstrate that Cd99l2 inversely regulates the expression of immediate-early genes (IEGs), including Arc, Egr1, and c-Fos, by inhibiting the activity of the transcription factors CREB and SRF. Neuronal inactivation increases the transport of Cd99l2 to the cell surface from recycling endosomes, thereby enhancing Cd99l2-mediated inhibitory signaling. Additionally, Cd99l2 knockout mice exhibit impaired excitatory synaptic transmission and plasticity in the hippocampus, along with deficits in spatial memory and contextual fear conditioning. Based on these findings, we propose that neuronal Cd99l2 functions as a synaptic cell adhesion molecule that inversely controls neuronal activation. |
| format | Article |
| id | doaj-art-0b2284c1fe0c48f588f1a08b35ea3424 |
| institution | Kabale University |
| issn | 2211-1247 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj-art-0b2284c1fe0c48f588f1a08b35ea34242025-01-14T04:12:03ZengElsevierCell Reports2211-12472025-01-01441115155Cd99l2 regulates excitatory synapse development and restrains immediate-early gene activationMinji Kang0Sang Ho Yoon1Minkyung Kang2Seung Pyo Park3Woo Seok Song4Jungho Kim5Seungha Lee6Da-ha Park7Jae-man Song8Beomsue Kim9Kyung Hee Park10Eun-Hye Joe11Hyun Goo Woo12Seong Hoe Park13Bong-Kiun Kaang14Dohyun Han15Yong-Seok Lee16Myoung-Hwan Kim17Young Ho Suh18Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, South Korea; Neuroscience Research Institute, Medical Research Center, Seoul National University, Seoul 03080, South Korea; Transplantation Research Institute, Medical Research Center, Seoul National University, Seoul 03080, South KoreaDepartment of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, South Korea; Neuroscience Research Institute, Medical Research Center, Seoul National University, Seoul 03080, South Korea; Department of Physiology, Seoul National University College of Medicine, Seoul 03080, South KoreaDepartment of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, South Korea; Neuroscience Research Institute, Medical Research Center, Seoul National University, Seoul 03080, South Korea; Department of Physiology, Seoul National University College of Medicine, Seoul 03080, South KoreaDepartment of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, South Korea; Neuroscience Research Institute, Medical Research Center, Seoul National University, Seoul 03080, South Korea; Transplantation Research Institute, Medical Research Center, Seoul National University, Seoul 03080, South KoreaDepartment of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, South Korea; Neuroscience Research Institute, Medical Research Center, Seoul National University, Seoul 03080, South Korea; Department of Physiology, Seoul National University College of Medicine, Seoul 03080, South KoreaDepartment of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, South Korea; Neuroscience Research Institute, Medical Research Center, Seoul National University, Seoul 03080, South Korea; Transplantation Research Institute, Medical Research Center, Seoul National University, Seoul 03080, South KoreaDepartment of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, South Korea; Neuroscience Research Institute, Medical Research Center, Seoul National University, Seoul 03080, South Korea; Transplantation Research Institute, Medical Research Center, Seoul National University, Seoul 03080, South KoreaDepartment of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, South Korea; Neuroscience Research Institute, Medical Research Center, Seoul National University, Seoul 03080, South Korea; Transplantation Research Institute, Medical Research Center, Seoul National University, Seoul 03080, South KoreaDepartment of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, South Korea; Neuroscience Research Institute, Medical Research Center, Seoul National University, Seoul 03080, South Korea; Transplantation Research Institute, Medical Research Center, Seoul National University, Seoul 03080, South KoreaNeural Circuits Research Group, Korea Brain Research Institute, Daegu 41062, South KoreaDepartment of Pharmacology, Ajou University School of Medicine, Suwon 16499, South KoreaDepartment of Pharmacology, Ajou University School of Medicine, Suwon 16499, South KoreaDepartment of Physiology, Ajou University School of Medicine, Suwon 16499, South KoreaTransplantation Research Institute, Medical Research Center, Seoul National University, Seoul 03080, South Korea; Department of Medicine, Seoul National University College of Medicine, Seoul 03080, South KoreaCenter for Cognition and Sociality, Life Science Institute, Institute for Basic Science (IBS), Daejeon 34126, South KoreaDepartment of Medicine, Seoul National University College of Medicine, Seoul 03080, South Korea; Department of Transdisciplinary Medicine, Seoul National University Hospital, Seoul 03080, South Korea; Corresponding authorDepartment of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, South Korea; Neuroscience Research Institute, Medical Research Center, Seoul National University, Seoul 03080, South Korea; Department of Physiology, Seoul National University College of Medicine, Seoul 03080, South Korea; Wide River Institute of Immunology, Seoul National University, Hongcheon 25159, South Korea; Corresponding authorDepartment of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, South Korea; Neuroscience Research Institute, Medical Research Center, Seoul National University, Seoul 03080, South Korea; Department of Physiology, Seoul National University College of Medicine, Seoul 03080, South Korea; Seoul National University Bundang Hospital, Seongnam, Gyeonggi 13620, South Korea; Corresponding authorDepartment of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, South Korea; Neuroscience Research Institute, Medical Research Center, Seoul National University, Seoul 03080, South Korea; Transplantation Research Institute, Medical Research Center, Seoul National University, Seoul 03080, South Korea; Corresponding authorSummary: Cd99 molecule-like 2 (Cd99l2) is a type I transmembrane protein that plays a role in the transmigration of leukocytes across vascular endothelial cells. Despite its high expression in the brain, the role of Cd99l2 remains elusive. We find that Cd99l2 is expressed primarily in neurons and positively regulates neurite outgrowth and the development of excitatory synapses. We demonstrate that Cd99l2 inversely regulates the expression of immediate-early genes (IEGs), including Arc, Egr1, and c-Fos, by inhibiting the activity of the transcription factors CREB and SRF. Neuronal inactivation increases the transport of Cd99l2 to the cell surface from recycling endosomes, thereby enhancing Cd99l2-mediated inhibitory signaling. Additionally, Cd99l2 knockout mice exhibit impaired excitatory synaptic transmission and plasticity in the hippocampus, along with deficits in spatial memory and contextual fear conditioning. Based on these findings, we propose that neuronal Cd99l2 functions as a synaptic cell adhesion molecule that inversely controls neuronal activation.http://www.sciencedirect.com/science/article/pii/S2211124724015067CP: NeuroscienceCP: Cell biology |
| spellingShingle | Minji Kang Sang Ho Yoon Minkyung Kang Seung Pyo Park Woo Seok Song Jungho Kim Seungha Lee Da-ha Park Jae-man Song Beomsue Kim Kyung Hee Park Eun-Hye Joe Hyun Goo Woo Seong Hoe Park Bong-Kiun Kaang Dohyun Han Yong-Seok Lee Myoung-Hwan Kim Young Ho Suh Cd99l2 regulates excitatory synapse development and restrains immediate-early gene activation Cell Reports CP: Neuroscience CP: Cell biology |
| title | Cd99l2 regulates excitatory synapse development and restrains immediate-early gene activation |
| title_full | Cd99l2 regulates excitatory synapse development and restrains immediate-early gene activation |
| title_fullStr | Cd99l2 regulates excitatory synapse development and restrains immediate-early gene activation |
| title_full_unstemmed | Cd99l2 regulates excitatory synapse development and restrains immediate-early gene activation |
| title_short | Cd99l2 regulates excitatory synapse development and restrains immediate-early gene activation |
| title_sort | cd99l2 regulates excitatory synapse development and restrains immediate early gene activation |
| topic | CP: Neuroscience CP: Cell biology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124724015067 |
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