Intraflagellar Transport Complex B Proteins Regulate the Hippo Effector Yap1 during Cardiogenesis.
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
YAP-Signaling Proteins
Zebrafish
/ embryology
Zebrafish Proteins
/ metabolism
BMP
Hippo
Intraflagellar transport (IFT)
Yap1
cargiogenesis
primary cilia
proepicardium
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
21 07 2020
21 07 2020
Historique:
received:
24
10
2019
revised:
30
04
2020
accepted:
29
06
2020
entrez:
23
7
2020
pubmed:
23
7
2020
medline:
29
4
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32698004
pii: S2211-1247(20)30913-X
doi: 10.1016/j.celrep.2020.107932
pii:
doi:
Substances chimiques
Adaptor Proteins, Signal Transducing
0
Bone Morphogenetic Proteins
0
Carrier Proteins
0
Cell Cycle Proteins
0
Trans-Activators
0
YAP-Signaling Proteins
0
Yap1 protein, mouse
0
Yes-associated protein (yap), zebrafish
0
Zebrafish Proteins
0
Protein Serine-Threonine Kinases
EC 2.7.11.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
107932Informations de copyright
Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests The authors declare no competing interests.