Extracellular Pgk1 interacts neural membrane protein enolase-2 to improve the neurite outgrowth of motor neurons
Abstract Understanding the molecular interaction between ligand and receptor is important for providing the basis for the development of regenerative drugs. Although it has been reported that extracellular phosphoglycerate kinase 1 (Pgk1) can promote the neurite outgrowth of motoneurons, the Pgk1-in...
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Nature Portfolio
2023-08-01
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Series: | Communications Biology |
Online Access: | https://doi.org/10.1038/s42003-023-05223-0 |
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author | Chuan-Yang Fu Hong-Yu Chen Cheng-Yung Lin Shiang-Jiuun Chen Jin-Chuan Sheu Huai-Jen Tsai |
author_facet | Chuan-Yang Fu Hong-Yu Chen Cheng-Yung Lin Shiang-Jiuun Chen Jin-Chuan Sheu Huai-Jen Tsai |
author_sort | Chuan-Yang Fu |
collection | DOAJ |
description | Abstract Understanding the molecular interaction between ligand and receptor is important for providing the basis for the development of regenerative drugs. Although it has been reported that extracellular phosphoglycerate kinase 1 (Pgk1) can promote the neurite outgrowth of motoneurons, the Pgk1-interacting neural receptor remains unknown. Here we show that neural membranous Enolase-2 exhibits strong affinity with recombinant Pgk1-Flag, which is also evidently demonstrated by immunoelectron microscopy. The 325th-417th domain of Pgk1 interacts with the 405th-431st domain of Enolase-2, but neither Enolase-1 nor Enolase-3, promoting neurite outgrowth. Combining Pgk1 incubation and Enolase-2 overexpression, we demonstrate a highly significant enhancement of neurite outgrowth of motoneurons through a reduced p-P38-T180/p-Limk1-S323/p-Cofilin signaling. Collectively, extracellular Pgk1 interacts neural membrane receptor Enolase-2 to reduce the P38/Limk1/Cofilin signaling which results in promoting neurite outgrowth. The extracellular Pgk1-specific neural receptor found in this study should provide a material for screening potential small molecule drugs that promote motor nerve regeneration. |
first_indexed | 2024-03-10T17:14:46Z |
format | Article |
id | doaj.art-f4d0238af9a34f19aa3f05bc23e4b239 |
institution | Directory Open Access Journal |
issn | 2399-3642 |
language | English |
last_indexed | 2024-03-10T17:14:46Z |
publishDate | 2023-08-01 |
publisher | Nature Portfolio |
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series | Communications Biology |
spelling | doaj.art-f4d0238af9a34f19aa3f05bc23e4b2392023-11-20T10:33:32ZengNature PortfolioCommunications Biology2399-36422023-08-016111410.1038/s42003-023-05223-0Extracellular Pgk1 interacts neural membrane protein enolase-2 to improve the neurite outgrowth of motor neuronsChuan-Yang Fu0Hong-Yu Chen1Cheng-Yung Lin2Shiang-Jiuun Chen3Jin-Chuan Sheu4Huai-Jen Tsai5Department of Life Science, Fu Jen Catholic UniversityInstitute of Molecular and Cellular Biology, National Taiwan UniversityInstitute of Biomedical Sciences, MacKay Medical CollegeDepartment of Life Science and Institute of Ecology and Evolutionary Biology, National Taiwan UniversityLiver Disease Prevention and Treatment Research FoundationDepartment of Life Science, Fu Jen Catholic UniversityAbstract Understanding the molecular interaction between ligand and receptor is important for providing the basis for the development of regenerative drugs. Although it has been reported that extracellular phosphoglycerate kinase 1 (Pgk1) can promote the neurite outgrowth of motoneurons, the Pgk1-interacting neural receptor remains unknown. Here we show that neural membranous Enolase-2 exhibits strong affinity with recombinant Pgk1-Flag, which is also evidently demonstrated by immunoelectron microscopy. The 325th-417th domain of Pgk1 interacts with the 405th-431st domain of Enolase-2, but neither Enolase-1 nor Enolase-3, promoting neurite outgrowth. Combining Pgk1 incubation and Enolase-2 overexpression, we demonstrate a highly significant enhancement of neurite outgrowth of motoneurons through a reduced p-P38-T180/p-Limk1-S323/p-Cofilin signaling. Collectively, extracellular Pgk1 interacts neural membrane receptor Enolase-2 to reduce the P38/Limk1/Cofilin signaling which results in promoting neurite outgrowth. The extracellular Pgk1-specific neural receptor found in this study should provide a material for screening potential small molecule drugs that promote motor nerve regeneration.https://doi.org/10.1038/s42003-023-05223-0 |
spellingShingle | Chuan-Yang Fu Hong-Yu Chen Cheng-Yung Lin Shiang-Jiuun Chen Jin-Chuan Sheu Huai-Jen Tsai Extracellular Pgk1 interacts neural membrane protein enolase-2 to improve the neurite outgrowth of motor neurons Communications Biology |
title | Extracellular Pgk1 interacts neural membrane protein enolase-2 to improve the neurite outgrowth of motor neurons |
title_full | Extracellular Pgk1 interacts neural membrane protein enolase-2 to improve the neurite outgrowth of motor neurons |
title_fullStr | Extracellular Pgk1 interacts neural membrane protein enolase-2 to improve the neurite outgrowth of motor neurons |
title_full_unstemmed | Extracellular Pgk1 interacts neural membrane protein enolase-2 to improve the neurite outgrowth of motor neurons |
title_short | Extracellular Pgk1 interacts neural membrane protein enolase-2 to improve the neurite outgrowth of motor neurons |
title_sort | extracellular pgk1 interacts neural membrane protein enolase 2 to improve the neurite outgrowth of motor neurons |
url | https://doi.org/10.1038/s42003-023-05223-0 |
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