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Published on: April 18, 2025
The nuclear receptor hepatocyte nuclear factor 4alpha acts as a morphogen to induce the formation of microvilli
Hideki Chiba1, Naoyuki Sakai, Masaki Murata
1Department of Pathology, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan. hidchiba@sapmed.ac.jp
Abstract:
Microvilli are actin-based organelles found on apical plasma membranes that are involved in nutrient uptake and signal transduction. Numerous components, including ezrin/radixin/moesin (ERM) proteins, have been identified that link filamentous actins to transmembrane proteins, but the signals driving microvillus biogenesis are not known. In this study, we show that the conditional and/or ectopic expression of a nuclear receptor, hepatocyte nuclear factor 4alpha (HNF4alpha), triggers microvillus morphogenesis. We also demonstrate that HNF4alpha expression induces ERM-binding phosphoprotein 50 (EBP50) expression and that attenuation of EBP50 using RNA interference inhibits microvillus development. We conclude that HNF4alpha acts as a morphogen to trigger microvillus formation.
Insights
Hepatocyte nuclear factor 4alpha (HNF4alpha) triggers microvillus formation by inducing ERM-binding phosphoprotein 50 (EBP50) expression. This nuclear receptor acts as a morphogen, initiating microvillus biogenesis.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Microvilli are essential actin-based apical structures involved in nutrient absorption and signaling.
- While proteins like ERM link actin to transmembrane proteins, the signals initiating microvillus biogenesis remain unclear.
Purpose of the Study:
- To investigate the role of nuclear receptors in microvillus morphogenesis.
- To identify signaling pathways involved in the formation of microvilli.
Main Methods:
- Conditional and ectopic expression of hepatocyte nuclear factor 4alpha (HNF4alpha).
- RNA interference (RNAi) to attenuate ERM-binding phosphoprotein 50 (EBP50) expression.
- Microscopic analysis of microvillus development.
Main Results:
- HNF4alpha expression was found to trigger microvillus morphogenesis.
- HNF4alpha induces the expression of EBP50.
- Inhibition of EBP50 via RNAi blocked microvillus development.
Conclusions:
- HNF4alpha acts as a morphogen, initiating microvillus formation.
- The HNF4alpha-EBP50 axis is crucial for microvillus biogenesis.
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