Essential role of ATP6AP2 enrichment in caveolae/lipid raft microdomains for the induction of neuronal differentiation of stem cells

Stem Cell Research & Therapy
Nehman MakdissyZiad Fajloun

Abstract

The subcellular distribution of prorenin receptor and adaptor protein ATP6AP2 may affect neurogenesis. In this study, we hypothesized that ATP6AP2 expression and subcellular relocalization from caveolae/lipid raft microdomains (CLR-Ms) to intracellular sites may correlate with neuronal differentiation (Neu-Dif) of adipose-derived mesenchymal stem cells (ADSCs). Human ADSCs isolated from 24 healthy donors and 24 patients with neurological disorders (ND) were cultured and induced for Neu-Dif. The mechanism of action of ATP6AP2 and the impact of its localization within the plasma membrane (particularly CLR-Ms) and intracellular sites on several pathways (mitogen-activated protein kinase, Wnt(s) signaling and others) and intracellular calcium and exosome release were evaluated. The impact of CLR-Ms on ATP6AP2 or vice versa was determined by pharmacological disruption of CLR-Ms or siATP6AP2 assays. In patients with ND, loss of ATP6AP2 from CLR-Ms correlated with an inhibition of Neu-Dif and signaling. However, its relocalization in CLR-Ms was positively correlated to induction of Neu-Dif in healthy subjects. An apparent switch from canonical to noncanonical Wnt signaling as well as from caveolin to flotillin occurs concurrently with...Continue Reading

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Citations

Jul 19, 2020·Reviews in the Neurosciences·Ge WangMujun Liu
Aug 29, 2019·BMC Molecular and Cell Biology·Kei Hanafusa, Nobuhiro Hayashi
Oct 17, 2018·Neural Regeneration Research·Alexander Bracke, Oliver von Bohlen Und Halbach
Sep 15, 2020·Frontiers in Molecular Neuroscience·Michihiro IgarashiMotohiro Nozumi
Feb 15, 2019·Neural Regeneration Research·Cheng-Cheng YingXin-Min Zheng
Jul 18, 2021·Journal of Orthopaedic Surgery and Research·Xiao-Hua LiHong-Lin Shen
Sep 10, 2021·Journal of Cancer Research and Clinical Oncology·Xingning LaiLixia Xiong

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Datasets Mentioned

BETA
GM130

Methods Mentioned

BETA
gene knockdown
biopsy
ELISA
flow cytometry
fluorescence microscopy
electrophoresis
transfection
confocal microscopy
co-IP

Software Mentioned

CLR
MACSQuant

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