ZFIN ID: ZDB-PUB-200724-16
Intraflagellar Transport Complex B Proteins Regulate the Hippo Effector Yap1 during Cardiogenesis
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.
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:
  • Adaptor Proteins, Signal Transducing/metabolism*
  • Animals
  • Biological Transport
  • Bone Morphogenetic Proteins/metabolism
  • Carrier Proteins/metabolism*
  • Cell Cycle Proteins/metabolism*
  • Cilia/metabolism
  • Flagella/metabolism*
  • HEK293 Cells
  • HeLa Cells
  • Heart/embryology*
  • Humans
  • Mice, Inbred C57BL
  • Organogenesis*
  • Pericardium/metabolism
  • Protein Binding
  • Protein Serine-Threonine Kinases/metabolism*
  • Signal Transduction
  • Trans-Activators/metabolism*
  • Zebrafish/embryology*
  • Zebrafish Proteins/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.
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