Journal
ELIFE
Volume 8, Issue -, Pages -Publisher
ELIFE SCIENCES PUBLICATIONS LTD
DOI: 10.7554/eLife.50850
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Funding
- National Research Foundation of Korea [2015M3C7A1030964, 2017M3C7A1047875, 2017R1A5A1015366, 2017R1A2B2009031]
- Ministry of Science, ICT and Future Planning [19-BR-02-01]
- Canadian Institutes of Health Research
- National Research Foundation of Korea [2017R1A5A1015366, 2015M3C7A1030964, 2017M3C7A1047875, 2017R1A2B2009031] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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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 GSK3 beta. TARA, an interaction partner of NDEL1, scaffolds DYRK2 and GSK3 beta 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-GSK3 beta complex as a novel regulatory mechanism underlying neuronal morphogenesis.
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