Wnt-5a Promotes Neural Development and Differentiation by Regulating CDK5 via Ca2+/Calpain Pathway
| Autor: | Qian Zhang, Min Xiang, Feng He, Ze-Xi Lv, Zheng Zhang, Xiang Peng, Bo Tian, Guangjian Qi, Hongwei Cai, Yang Shu, Pei Zhang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Physiology Neurogenesis Cellular differentiation Cyclin D Cyclin-dependent kinase 5 Development Wnt-5a Protein lcsh:Physiology lcsh:Biochemistry 03 medical and health sciences Animals lcsh:QD415-436 Kinase activity Cells Cultured Neurons biology lcsh:QP1-981 Calpain Chemistry Ca2+/calpain signaling Cyclin-dependent kinase 2 Wnt signaling pathway Cell cycle Wnt signaling Rats Cell biology 030104 developmental biology nervous system Differentiation biology.protein Calcium Signal Transduction |
| Zdroj: | Cellular Physiology and Biochemistry, Vol 51, Iss 6, Pp 2604-2615 (2018) |
| ISSN: | 1421-9778 1015-8987 |
| Popis: | Background/Aims: The Wnt signaling pathway has essential functions in the central nervous system, where it regulates the major physiological functions of neurons, including development, differentiation, and plasticity. Wnt signaling controls these cellular events; however, how Wnt pathways integrate into a coherent developmental program remains unclear. Methods: The expression and secretion of different WNT ligands (Wnt-1, Wnt-3a, Wnt-4, Wnt-5a, Wnt-11), and the levels and activities of cyclin-dependent kinases (CDK2, CDK4, CDK6/cyclin D, cyclin E) or CDK5 (CDK5/p35 and p25) were measured in Rat cortex at different embryonic stages, and in RA/BDNF-induced differentiated SH-SY5Y cell model, by Quantitative real-time PCR (qPCR), western blotting, ELISA, and in vitro CDK5 kinase assays. MAP2-BrdU double staining was used to assess cell differentiation and cell cycle exit in an RA/BDNF-induced differentiated SH-SY5Y cell model. The effects of CDK5 and Ca2+/calpain signaling were assessed using specific chemical inhibitors. Results: We found that Wnt-1 was unchanged and Wnt-3a was attenuated, whereas Wnt-4, Wnt-5a, and Wnt-11 were markedly up-regulated, during the development of neurons and differentiated SH-SY5Y cells. Simultaneously, the activity of CDK5 was elevated. Furthermore, we describe crosstalk between non-canonical Wnt signaling and CDK5 in the development of neurons and differentiated SH-SY5Y cells. Wnt-5a, a non-canonical Wnt ligand, regulated CDK5 via Ca2+/calpain signaling in both neuronal development and differentiation. Inhibition of Wnt-5a diminished CDK5 kinase activity via the Ca2+/calpain pathway, thereby attenuating RA-BDNF induced SH-SY5Y cell differentiation. Conclusion: Wnt-5a signaling is a significant regulator of neuronal development and differentiation and upregulates CDK5 kinase activity via Ca2+/calpain signaling. |
| Databáze: | OpenAIRE |
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