Sequential phosphorylation of NDEL1 by the DYRK2-GSK3β complex is critical for neuronal morphogenesis

التفاصيل البيبلوغرافية
العنوان: Sequential phosphorylation of NDEL1 by the DYRK2-GSK3β complex is critical for neuronal morphogenesis
المؤلفون: Seunghyun Kim, Su-Jin Noh, Minh Dang Nguyen, Bo Kyoung Suh, Ji-Ho Hong, Truong Thi My Nhung, Sang Ki Park, Yongdo Kwak, Hyun-Jin Jung, Soo Jeong Kim, Dong Jin Mun, Ahryoung Lee, Youngshik Choe, Youngsik Woo, Seung Tae Baek
المصدر: eLife
eLife, Vol 8 (2019)
سنة النشر: 2019
مصطلحات موضوعية: Proteome, Mouse, neuronal arborization, Mice, 0302 clinical medicine, Morphogenesis, Kinome, Neuronal Arborization, Biology (General), Phosphorylation, Neurons, 0303 health sciences, Chemistry, General Neuroscience, Microfilament Proteins, General Medicine, Protein-Tyrosine Kinases, Cell biology, Medicine, Research Article, QH301-705.5, Science, TARA-DYRK2-GSK3β complex, macromolecular substances, Protein Serine-Threonine Kinases, Filamentous actin, General Biochemistry, Genetics and Molecular Biology, filamentous actin dynamics, 03 medical and health sciences, neuronal morphogenesis, Animals, Humans, 030304 developmental biology, Glycogen Synthase Kinase 3 beta, General Immunology and Microbiology, NDEL1, Mechanism (biology), Neuronal morphogenesis, nervous system, axon/dendrite outgrowth, NDEL1 phosphorylation, Rat, Carrier Proteins, Developmental biology, Protein Processing, Post-Translational, 030217 neurology & neurosurgery, Developmental Biology, Neuroscience
الوصف: Neuronal morphogenesis requires multiple regulatory pathways to appropriately determine axonal and dendritic structures, thereby to enable the functional neural connectivity. Yet, however, the precise mechanisms and components that regulate neuronal morphogenesis are still largely unknown. Here, we newly identified the sequential phosphorylation of NDEL1 critical for neuronal morphogenesis through the human kinome screening and phospho-proteomics analysis of NDEL1 from mouse brain lysate. DYRK2 phosphorylates NDEL1 S336 to prime the phosphorylation of NDEL1 S332 by GSK3β. TARA, an interaction partner of NDEL1, scaffolds DYRK2 and GSK3β to form a tripartite complex and enhances NDEL1 S336/S332 phosphorylation. This dual phosphorylation increases the filamentous actin dynamics. Ultimately, the phosphorylation enhances both axonal and dendritic outgrowth and promotes their arborization. Together, our findings suggest the NDEL1 phosphorylation at S336/S332 by the TARA-DYRK2-GSK3β complex as a novel regulatory mechanism underlying neuronal morphogenesis.
تدمد: 2050-084X
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6d4056daa75e98ce571bf3b39bd2a683
https://pubmed.ncbi.nlm.nih.gov/31815665
حقوق: OPEN
رقم الأكسشن: edsair.doi.dedup.....6d4056daa75e98ce571bf3b39bd2a683
قاعدة البيانات: OpenAIRE