p39-associated Cdk5 activity regulates dendritic morphogenesis
Autor: | Amy K.Y. Fu, Yuewen Chen, Wing Yu Fu, Ye Wang, Li Ouyang, Yu Chen, Nancy Y. Ip |
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Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
Blotting
Western Morphogenesis Regulator lcsh:Medicine Biology Neurotransmission Real-Time Polymerase Chain Reaction Nervous System Synaptic Transmission Mass Spectrometry Article Mice Phosphatidylinositol 3-Kinases Cyclic AMP Animals Humans lcsh:Science Protein kinase B PI3K/AKT/mTOR pathway Adaptor Proteins Signal Transducing Lipid-Linked Proteins Monomeric GTP-Binding Proteins Neurons Multidisciplinary Cyclin-dependent kinase 5 HEK 293 cells lcsh:R Signal transducing adaptor protein Cell Differentiation Cyclin-Dependent Kinase 5 Development of the nervous system Dendrites Cellular neuroscience Cell biology Cytoskeletal Proteins HEK293 Cells nervous system lcsh:Q Proto-Oncogene Proteins c-akt Signal Transduction |
Zdroj: | Scientific Reports, Vol 10, Iss 1, Pp 1-16 (2020) Scientific Reports |
ISSN: | 2045-2322 |
DOI: | 10.1038/s41598-020-75264-6 |
Popis: | Dendrites, branched structures extending from neuronal cell soma, are specialized for processing information from other neurons. The morphogenesis of dendritic structures is spatiotemporally regulated by well-orchestrated signaling cascades. Dysregulation of these processes impacts the wiring of neuronal circuit and efficacy of neurotransmission, which contribute to the pathogeneses of neurological disorders. While Cdk5 (cyclin-dependent kinase 5) plays a critical role in neuronal dendritic development, its underlying molecular control is not fully understood. In this study, we show that p39, one of the two neuronal Cdk5 activators, is a key regulator of dendritic morphogenesis. Pyramidal neurons deficient in p39 exhibit aberrant dendritic morphology characterized by shorter length and reduced arborization, which is comparable to dendrites in Cdk5-deficient neurons. RNA sequencing analysis shows that the adaptor protein, WDFY1 (WD repeat and FYVE domain-containing 1), acts downstream of Cdk5/p39 to regulate dendritic morphogenesis. While WDFY1 is elevated in p39-deficient neurons, suppressing its expression rescues the impaired dendritic arborization. Further phosphoproteomic analysis suggests that Cdk5/p39 mediates dendritic morphogenesis by modulating various downstream signaling pathways, including PI3K/Akt-, cAMP-, or small GTPase-mediated signaling transduction pathways, thereby regulating cytoskeletal organization, protein synthesis, and protein trafficking. |
Databáze: | OpenAIRE |
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