Glial cell-line derived neurotrophic factor and neurturin regulate the expressions of distinct miRNA precursors through the activation of GFRalpha2.
Glial cell line-derived neurotrophic factor (GDNF) and neurturin (NTN) are structurally related neurotrophic factors that have both been shown to prevent the degeneration of dopaminergic neurons in vitro and in vivo. NTN and GDNF are thought to bind with different affinities to the GDNF family receptor alpha-2 (GFRalpha2), and can activate the same multi-component receptor system consisting of GFRalpha2, receptor tyrosine kinase Ret (RET) and NCAM. MicroRNAs (miRNAs) are a class of short, non-coding RNAs that regulate gene expression through translational repression or RNA degradation. miRNAs have diverse functions, including regulating differentiation, proliferation and apoptosis in several organisms. It is currently unknown whether GDNF and NTN regulate the expression of miRNAs through activation of the same multi-component receptor system. Using quantitative real-time PCR, we measured the expression of some miRNA precursors in human BE(2)-C cells that express GFRalpha2 but not GFRalpha1. GDNF and NTN differentially regulate the expression of distinct miRNA precursors through the activation of mitogen-activated protein kinase (extracellular signal-regulated kinase 1/2). This study showed that the expression of distinct miRNA precursors is differentially regulated by specific ligands through the activation of GFRalpha2.
Yoong
Li Foong
LF
Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Wan
Guoqiang
G
Too
Heng-Phon
HP
D002478:Cells, Cultured; D004789:Enzyme Activation / Q000502:physiology; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D008928:Mitochondria / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology; D019006:Neural Cell Adhesion Molecules / Q000378:metabolism; D051101:Neurturin / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D010766:Phosphorylation; D012313:RNA / Q000096:biosynthesis*; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology
D051100:Glial Cell Line-Derived Neurotrophic Factor; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D008024:Ligands; D019006:Neural Cell Adhesion Molecules; D051101:Neurturin; D012313:RNA; D020794:Receptor Protein-Tyrosine Kinases; D020928:Mitogen-Activated Protein Kinases