The nuclear receptor hepatocyte nuclear factor 4alpha acts as a morphogen to induce the formation of microvilli.
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.
Chiba
Hideki
H
Department of Pathology, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan. hidchiba@sapmed.ac.jp
Sakai
Naoyuki
N
Murata
Masaki
M
Osanai
Makoto
M
Ninomiya
Takafumi
T
Kojima
Takashi
T
Sawada
Norimasa
N
D000818:Animals; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D051557:Hepatocyte Nuclear Factor 4 / Q000235:genetics / Q000378:metabolism*; D015151:Immunoblotting; D007124:Immunoenzyme Techniques; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008840:Microfilament Proteins / Q000378:metabolism; D008871:Microvilli / Q000378:metabolism*; D009024:Morphogenesis; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism; D010750:Phosphoproteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D047490:Retinoid X Receptor alpha / Q000378:metabolism; D047491:Retinoid X Receptor gamma / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology; D000099149:Ezrin
D003598:Cytoskeletal Proteins; D051557:Hepatocyte Nuclear Factor 4; D008565:Membrane Proteins; D008840:Microfilament Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D047490:Retinoid X Receptor alpha; D047491:Retinoid X Receptor gamma; D017923:Sodium-Hydrogen Exchangers; D014212:Tretinoin; D000099149:Ezrin; C496594:Hnf4a protein, rat; C093376:sodium-hydrogen exchanger regulatory factor; C071058:moesin; C071776:radixin