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2017 ; 8
(ä): 14582
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English Wikipedia
Amotl1 mediates sequestration of the Hippo effector Yap1 downstream of Fat4 to
restrict heart growth
#MMPMID28239148
Ragni CV
; Diguet N
; Le Garrec JF
; Novotova M
; Resende TP
; Pop S
; Charon N
; Guillemot L
; Kitasato L
; Badouel C
; Dufour A
; Olivo-Marin JC
; Trouvé A
; McNeill H
; Meilhac SM
Nat Commun
2017[Feb]; 8
(ä): 14582
PMID28239148
show ga
Although in flies the atypical cadherin Fat is an upstream regulator of Hippo
signalling, the closest mammalian homologue, Fat4, has been shown to regulate
tissue polarity rather than growth. Here we show in the mouse heart that Fat4
modulates Hippo signalling to restrict growth. Fat4 mutant myocardium is thicker,
with increased cardiomyocyte size and proliferation, and this is mediated by an
upregulation of the transcriptional activity of Yap1, an effector of the Hippo
pathway. Fat4 is not required for the canonical activation of Hippo kinases but
it sequesters a partner of Yap1, Amotl1, out of the nucleus. The nuclear
translocation of Amotl1 is accompanied by Yap1 to promote cardiomyocyte
proliferation. We, therefore, identify Amotl1, which is not present in flies, as
a mammalian intermediate for non-canonical Hippo signalling, downstream of Fat4.
This work uncovers a mechanism for the restriction of heart growth at birth, a
process which impedes the regenerative potential of the mammalian heart.
|Adaptor Proteins, Signal Transducing/*metabolism
[MESH]