关于Sema3F在神经元的受体研究
Study on the Receptor of Sema3F in Neurons
DOI: 10.12677/md.2025.151005, PDF,    国家自然科学基金支持
作者: 张顺禹*, 贾凯茹*, 杨雨佳, 杨泽睿, 胡可鑫：内蒙古医科大学第一临床医学院，内蒙古 呼和浩特；杨光路#：内蒙古医科大学附属医院儿科，内蒙古 呼和浩特
关键词: 信号素；神经元；神经纤毛蛋白；Signaling； Neuron； Neurofibromin
摘要: Sema3F是一种在多种神经类疾病中起重要作用的信号素，其在神经元内的受体研究对于治疗这类疾病具有潜在的临床意义。文章重点探讨了Sema3F通过其全受体复合物，包括神经纤毛蛋白-2 (Neuropilin-2, NRP2)和丛蛋白A3 (PlexinA3)来传递信号，并参与引导神经元以及调节免疫反应、炎症和宿主防御。研究还发现Sema3F与NRP-2的结合亲和力高于NRP-1，且Sema3家族成员需要通过弗林蛋白酶的水解加工才能与NRP1竞争性结合，揭示了Sema3活性的新型调节机制。这些发现对于理解Sema3F在神经系统中的作用及其在疾病治疗中的潜在应用具有重要意义。
Abstract: Sema3F is a signaling that plays an important role in a variety of neurological diseases. The study of its receptor in the menstrual cells has potential clinical significance for the treatment of such diseases. The paper focuses on Sema3F to transmit signals through its full receptor complex, including Neurofibromalin-2, NRP2, and plexinA3 and is involved in guiding neurons as well as regulating immune response, inflammation, and host defense. The study also found that Sema3F has a higher binding affinity with NRP-2 than NRP-1 and that members of the Sema3 family need to be hydrolyzed by Flynne enzyme to competitively bind to NRP1, revealing a novel regulatory mechanism of Sema3 activity. These findings have important implications for understanding the role of Sema3F in the nervous system and its potential use in disease therapy.
文章引用：张顺禹, 贾凯茹, 杨雨佳, 杨泽睿, 胡可鑫, 杨光路. 关于Sema3F在神经元的受体研究[J]. 医学诊断, 2025, 15(1): 28-32. https://doi.org/10.12677/md.2025.151005

参考文献

[1] Koropouli, E., Wang, Q., Mejías, R., Hand, R., Wang, T., Ginty, D.D., et al. (2023) Palmitoylation Regulates Neuropilin-2 Localization and Function in Cortical Neurons and Conveys Specificity to Semaphorin Signaling via Palmitoyl Acyltransferases. eLife, 12, e83217. [Google Scholar] [CrossRef] [PubMed]
[2] Kotan, L.D., Ternier, G., Cakir, A.D., Emeksiz, H.C., Turan, I., Delpouve, G., et al. (2021) Loss-of-Function Variants in SEMA3F and PLXNA3 Encoding Semaphorin-3f and Its Receptor Plexin-A3 Respectively Cause Idiopathic Hypogonadotropic Hypogonadism. Genetics in Medicine, 23, 1008-1016. [Google Scholar] [CrossRef] [PubMed]
[3] Nasarre, P., Constantin, B., Rouhaud, L., Harnois, T., Raymond, G., Drabkin, H.A., et al. (2003) Semaphorin SEMA3F and VEGF Have Opposing Effects on Cell Attachment and Spreading. Neoplasia, 5, 83-92. [Google Scholar] [CrossRef] [PubMed]
[4] Guo, H., Li, X., Parker, M.W., Waltenberger, J., Becker, P.M. and Vander Kooi, C.W. (2013) Mechanistic Basis for the Potent Anti-Angiogenic Activity of Semaphorin 3F. Biochemistry, 52, 7551-7558. [Google Scholar] [CrossRef] [PubMed]
[5] Shiflett, M.W., Gavin, M. and Tran, T.S. (2015) Altered Hippocampal-Dependent Memory and Motor Function in Neuropilin 2-Deficient Mice. Translational Psychiatry, 5, e521-e521. [Google Scholar] [CrossRef] [PubMed]
[6] Parker, M.W., Linkugel, A.D. and Vander Kooi, C.W. (2013) Effect of C-Terminal Sequence on Competitive Semaphorin Binding to Neuropilin-1. Journal of Molecular Biology, 425, 4405-4414. [Google Scholar] [CrossRef] [PubMed]
[7] Takeuchi, H., Inokuchi, K., Aoki, M., Suto, F., Tsuboi, A., Matsuda, I., et al. (2010) Sequential Arrival and Graded Secretion of Sema3F by Olfactory Neuron Axons Specify Map Topography at the Bulb. Cell, 141, 1056-1067. [Google Scholar] [CrossRef] [PubMed]
[8] Moragas, N., Fernandez-Nogueira, P., Recalde-Percaz, L., Inman, J.L., López-Plana, A., Bergholtz, H., et al. (2024) The SEMA3F-NRP1/NRP2 Axis Is a Key Factor in the Acquisition of Invasive Traits in in Situ Breast Ductal Carcinoma. Breast Cancer Research, 26, Article No. 122. [Google Scholar] [CrossRef] [PubMed]
[9] Ye, K., Ouyang, X., Wang, Z., Yao, L. and Zhang, G. (2020) SEMA3F Promotes Liver Hepatocellular Carcinoma Metastasis by Activating Focal Adhesion Pathway. DNA and Cell Biology, 39, 474-483. [Google Scholar] [CrossRef] [PubMed]
[10] Nakayama, H., Bruneau, S., Kochupurakkal, N., Coma, S., Briscoe, D.M. and Klagsbrun, M. (2015) Regulation of mTOR Signaling by Semaphorin 3F-Neuropilin 2 Interactions in vitro and in vivo. Scientific Reports, 5, Article No. 11789. [Google Scholar] [CrossRef] [PubMed]
[11] Doçi, C.L., Mikelis, C.M., Lionakis, M.S., Molinolo, A.A. and Gutkind, J.S. (2015) Genetic Identification of SEMA3F as an Antilymphangiogenic Metastasis Suppressor Gene in Head and Neck Squamous Carcinoma. Cancer Research, 75, 2937-2948. [Google Scholar] [CrossRef] [PubMed]
[12] Knipper, K., Lyu, S.I., Jung, J., Alich, N., Popp, F.C., Schröder, W., et al. (2024) Semaphorin 3F (SEMA3F) Influences Patient Survival in Esophageal Adenocarcinoma. Scientific Reports, 14, Article No. 20589. [Google Scholar] [CrossRef] [PubMed]
[13] 殷善开, 编. 感官系统[M]. 上海: 上海交通大学出版社, 2021, 174.
[14] Curreli, S., Wong, B.S., Latinovic, O., Konstantopoulos, K. and Stamatos, N.M. (2016) Class 3 Semaphorins Induce F-Actin Reorganization in Human Dendritic Cells: Role in Cell Migration. Journal of Leukocyte Biology, 100, 1323-1334. [Google Scholar] [CrossRef] 
[15] Osborne, N.J., Begbie, J., Chilton, J.K., Schmidt, H. and Eickholt, B.J. (2005) Semaphorin/Neuropilin Signaling Influences the Positioning of Migratory Neural Crest Cells within the Hindbrain Region of the Chick. Developmental Dynamics, 232, 939-949. [Google Scholar] [CrossRef] [PubMed]
[16] Knipper, K., Lyu, S.I., Jung, J.-O., Alich, N., Popp, F.C., Schröder, W., et al. (2024) Semaphorin 3F (SEMA3F) Influences Patient Survival in Esophageal Adenocarcinoma. Scientific Reports, 14, Article No. 20589. [Google Scholar] [CrossRef] [PubMed]
[17] Shimizu, A., Mammoto, A., Italiano, J.E., Pravda, E., Dudley, A.C., Ingber, D.E., et al. (2008) ABL2/ARG Tyrosine Kinase Mediates SEMA3F-Induced Rhoa Inactivation and Cytoskeleton Collapse in Human Glioma Cells. Journal of Biological Chemistry, 283, 27230-27238. [Google Scholar] [CrossRef] [PubMed]
[18] Kotan, L.D., Ternier, G., Cakir, A.D., Emeksiz, H.C., Turan, I., Delpouve, G., et al. (2021) Loss-of-Function Variants in SEMA3F and PLXNA3 Encoding Semaphorin-3f and Its Receptor Plexin-A3 Respectively Cause Idiopathic Hypogonadotropic Hypogonadism. Genetics in Medicine, 23, 1008-1016. [Google Scholar] [CrossRef] [PubMed]
[19] Duncan, B.W., Mohan, V., Wade, S.D., Truong, Y., Kampov-Polevoi, A., Temple, B.R., et al. (2021) Semaphorin3f Drives Dendritic Spine Pruning through Rho-GTPase Signaling. Molecular Neurobiology, 58, 3817-3834. [Google Scholar] [CrossRef] [PubMed]
[20] Sijaona, A., Luukko, K., Kvinnsland, I.H. and Kettunen, P. (2011) Expression Patterns of Sema3F, PlexinA4,-A3, Neuropilin1 and-2 in the Postnatal Mouse Molar Suggest Roles in Tooth Innervation and Organogenesis. Acta Odontologica Scandinavica, 70, 140-148. [Google Scholar] [CrossRef] [PubMed]
[21] Demyanenko, G.P., Mohan, V., Zhang, X., Brennaman, L.H., Dharbal, K.E.S., Tran, T.S., et al. (2014) Neural Cell Adhesion Molecule Nrcam Regulates Semaphorin 3F-Induced Dendritic Spine Remodeling. The Journal of Neuroscience, 34, 11274-11287. [Google Scholar] [CrossRef] [PubMed]