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 SM, Vermot J.
Source : Cell Rep
2020 juil 21
Pmid / DOI: 32698004
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.