Vitamin D regulation of GDNF/Ret signaling in dopaminergic neurons

Pertile, Renata A. N., Cui, Xiaoying, Hammond, Luke and Eyles, Darryl W. (2018) Vitamin D regulation of GDNF/Ret signaling in dopaminergic neurons. The FASEB Journal, 32 2: fj201700713R-828. doi:10.1096/fj.201700713R

Author Pertile, Renata A. N.
Cui, Xiaoying
Hammond, Luke
Eyles, Darryl W.
Title Vitamin D regulation of GDNF/Ret signaling in dopaminergic neurons
Journal name The FASEB Journal   Check publisher's open access policy
ISSN 0892-6638
Publication date 2018-10-10
Year available 2018
Sub-type Article (original research)
DOI 10.1096/fj.201700713R
Open Access Status Not yet assessed
Volume 32
Issue 2
Start page fj201700713R
End page 828
Total pages 13
Place of publication Bethesda, MD, United States
Publisher Federation of American Societies for Experimental Biology
Language eng
Abstract 1,25(OH)2D3 (vitamin D) appears essential for the normal development of dopaminergic neurons. Vitamin D affects dopamine synthesis and metabolism as well as expression of glial cell line-derived neurotrophic factor (GDNF), which is crucial for the survival of dopaminergic neurons. We investigated the role of vitamin D on GDNF and its receptors protooncogene tyrosine-protein kinase receptor Ret (C-Ret) and GDNF family receptor alpha 1 (GFRα1) signaling. To this end, we used a developmental vitamin D-deficient rat model and SH-SY5Y cells transfected with vitamin D receptor (VDR). The absence of vitamin D ligand in gestation reduces C-Ret expression, but not GDNF and GFRα1, in embryo forebrains. Overexpression of VDR in SH-SY5Y in the absence of ligand (mimicking in vivo developmental vitamin D deficiency) also suppressed C-Ret mRNA levels. In the presence of vitamin D, C-Ret mRNA and protein expression were increased. The chromatin immunoprecipitation results suggested that C-Ret is directly regulated by vitamin D via VDR. GDNF was also increased by vitamin D in these cells. Our small interfering RNA studies showed that knocking down VDR leads to an increase in C-Ret in the absence of ligand. Finally, we confirmed the inverse relationship between GFRα1 and C-Ret, as knocking down C-Ret led to increases in GFRα1 expression. These data extend our knowledge of the diverse and important roles played by vitamin D in dopamine physiology.-Pertile, R. A. N., Cui, X., Hammond, L., Eyles, D. W. Vitamin D regulation of GDNF/Ret signaling in dopaminergic neurons.
Keyword C-Ret
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID APP1057883
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
Queensland Brain Institute Publications
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Created: Wed, 18 Oct 2017, 12:14:36 EST by Renata Aparecida Nedel Pertile on behalf of Queensland Brain Institute