دورية أكاديمية
p39-associated Cdk5 activity regulates dendritic morphogenesis.
| العنوان: | p39-associated Cdk5 activity regulates dendritic morphogenesis. |
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| المؤلفون: | Ouyang L; Division of Life Science, State Key Laboratory of Molecular Neuroscience and Molecular Neuroscience Center, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.; Hong Kong Center for Neurodegenerative Diseases, Hong Kong Science Park, Hong Kong, China., Chen Y; Division of Life Science, State Key Laboratory of Molecular Neuroscience and Molecular Neuroscience Center, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.; Hong Kong Center for Neurodegenerative Diseases, Hong Kong Science Park, Hong Kong, China.; The Brain Cognition and Brain Disease Institute, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen, 518055, Guangdong, China.; Guangdong Provincial Key Laboratory of Brain Science, Disease and Drug Development, HKUST Shenzhen Research Institute, Shenzhen-Hong Kong Institute of Brain Science, Shenzhen, 518057, Guangdong, China., Wang Y; Division of Life Science, State Key Laboratory of Molecular Neuroscience and Molecular Neuroscience Center, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.; Hong Kong Center for Neurodegenerative Diseases, Hong Kong Science Park, Hong Kong, China., Chen Y; Division of Life Science, State Key Laboratory of Molecular Neuroscience and Molecular Neuroscience Center, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.; Hong Kong Center for Neurodegenerative Diseases, Hong Kong Science Park, Hong Kong, China.; The Brain Cognition and Brain Disease Institute, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen, 518055, Guangdong, China.; Guangdong Provincial Key Laboratory of Brain Science, Disease and Drug Development, HKUST Shenzhen Research Institute, Shenzhen-Hong Kong Institute of Brain Science, Shenzhen, 518057, Guangdong, China., Fu AKY; Division of Life Science, State Key Laboratory of Molecular Neuroscience and Molecular Neuroscience Center, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.; Hong Kong Center for Neurodegenerative Diseases, Hong Kong Science Park, Hong Kong, China.; Guangdong Provincial Key Laboratory of Brain Science, Disease and Drug Development, HKUST Shenzhen Research Institute, Shenzhen-Hong Kong Institute of Brain Science, Shenzhen, 518057, Guangdong, China., Fu WY; Division of Life Science, State Key Laboratory of Molecular Neuroscience and Molecular Neuroscience Center, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.; Hong Kong Center for Neurodegenerative Diseases, Hong Kong Science Park, Hong Kong, China., Ip NY; Division of Life Science, State Key Laboratory of Molecular Neuroscience and Molecular Neuroscience Center, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China. boip@ust.hk.; Hong Kong Center for Neurodegenerative Diseases, Hong Kong Science Park, Hong Kong, China. boip@ust.hk.; Guangdong Provincial Key Laboratory of Brain Science, Disease and Drug Development, HKUST Shenzhen Research Institute, Shenzhen-Hong Kong Institute of Brain Science, Shenzhen, 518057, Guangdong, China. boip@ust.hk. |
| المصدر: | Scientific reports [Sci Rep] 2020 Oct 30; Vol. 10 (1), pp. 18746. Date of Electronic Publication: 2020 Oct 30. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: London : Nature Publishing Group, copyright 2011- |
| مواضيع طبية MeSH: | Cyclin-Dependent Kinase 5/*metabolism , Cytoskeletal Proteins/*metabolism , Dendrites/*metabolism , Lipid-Linked Proteins/*metabolism, Adaptor Proteins, Signal Transducing/genetics ; Adaptor Proteins, Signal Transducing/metabolism ; Animals ; Blotting, Western ; Cell Differentiation/genetics ; Cell Differentiation/physiology ; Cyclic AMP/metabolism ; Cyclin-Dependent Kinase 5/genetics ; Cytoskeletal Proteins/genetics ; HEK293 Cells ; Humans ; Lipid-Linked Proteins/genetics ; Mass Spectrometry ; Mice ; Monomeric GTP-Binding Proteins/genetics ; Monomeric GTP-Binding Proteins/metabolism ; Morphogenesis/genetics ; Morphogenesis/physiology ; Nervous System/cytology ; Nervous System/metabolism ; Neurons/metabolism ; Phosphatidylinositol 3-Kinases/genetics ; Phosphatidylinositol 3-Kinases/metabolism ; Proto-Oncogene Proteins c-akt/genetics ; Proto-Oncogene Proteins c-akt/metabolism ; Real-Time Polymerase Chain Reaction ; Signal Transduction/genetics ; Signal Transduction/physiology ; Synaptic Transmission/genetics ; Synaptic Transmission/physiology |
| مستخلص: | 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. |
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| المشرفين على المادة: | 0 (Adaptor Proteins, Signal Transducing) 0 (Cdk5r2 protein, mouse) 0 (Cytoskeletal Proteins) 0 (Lipid-Linked Proteins) 0 (Wdfy1 protein, mouse) E0399OZS9N (Cyclic AMP) EC 2.7.11.1 (Cyclin-Dependent Kinase 5) EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) EC 2.7.11.22 (Cdk5 protein, mouse) EC 3.6.5.2 (Monomeric GTP-Binding Proteins) |
| تواريخ الأحداث: | Date Created: 20201031 Date Completed: 20210301 Latest Revision: 20210301 |
| رمز التحديث: | 20231215 |
| مُعرف محوري في PubMed: | PMC7603351 |
| DOI: | 10.1038/s41598-020-75264-6 |
| PMID: | 33127972 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 2045-2322 |
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| DOI: | 10.1038/s41598-020-75264-6 |