PUBLICATION

Intraflagellar Transport Complex B Proteins Regulate the Hippo Effector Yap1 during Cardiogenesis

Authors
Peralta, M., Ortiz Lopez, L., Jerabkova, K., Lucchesi, T., Vitre, B., Han, D., Guillemot, L., Dingare, C., Sumara, I., Mercader, N., Lecaudey, V., Delaval, B., Meilhac, S.M., Vermot, J.
ID
ZDB-PUB-200724-16
Date
2020
Source
Cell Reports   32: 107932 (Journal)
Registered Authors
Han, Dong, Lecaudey, Virginie, Mercader Huber, Nadia, Peralta López, Marina, Vermot, Julien
Keywords
BMP, Hippo, Intraflagellar transport (IFT), Yap1, cargiogenesis, primary cilia, proepicardium
MeSH Terms
  • Pericardium/metabolism
  • Biological Transport
  • Protein Binding
  • Carrier Proteins/metabolism*
  • HeLa Cells
  • Animals
  • Protein Serine-Threonine Kinases/metabolism*
  • Cell Cycle Proteins/metabolism*
  • Organogenesis*
  • Signal Transduction
  • Zebrafish/embryology*
  • Adaptor Proteins, Signal Transducing/metabolism*
  • Heart/embryology*
  • Zebrafish Proteins/metabolism*
  • HEK293 Cells
  • Bone Morphogenetic Proteins/metabolism
  • Flagella/metabolism*
  • Mice, Inbred C57BL
  • Cilia/metabolism
  • Humans
  • Trans-Activators/metabolism*
PubMed
32698004 Full text @ Cell Rep.
Abstract
Cilia and the intraflagellar transport (IFT) proteins involved in ciliogenesis are associated with congenital heart diseases (CHDs). However, the molecular links between cilia, IFT proteins, and cardiogenesis are yet to be established. Using a combination of biochemistry, genetics, and live-imaging methods, we show that IFT complex B proteins (Ift88, Ift54, and Ift20) modulate the Hippo pathway effector YAP1 in zebrafish and mouse. We demonstrate that this interaction is key to restrict the formation of the proepicardium and the myocardium. In cellulo experiments suggest that IFT88 and IFT20 interact with YAP1 in the cytoplasm and functionally modulate its activity, identifying a molecular link between cilia-related proteins and the Hippo pathway. Taken together, our results highlight a noncanonical role for IFT complex B proteins during cardiogenesis and shed light on a mechanism of action for ciliary proteins in YAP1 regulation.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping