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LDL receptor‐related protein LRP 6 senses nutrient levels and regulates Hippo signaling
Author(s) -
Jeong Wonyoung,
Kim Soyoung,
Lee Ukjin,
Zhong Zhendong A,
Savitsky Mikhail,
Kwon Hyeryun,
Kim Jiyoung,
Lee Taebok,
Cho Jin Won,
Williams Bart O,
Katanaev Vladimir L,
Jho Eekhoon
Publication year - 2020
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.202050103
Subject(s) - library science , medicine , computer science
Controlled cell growth and proliferation are essential for tissue homeostasis and development. Wnt and Hippo signaling are well known as positive and negative regulators of cell proliferation, respectively. The regulation of Hippo signaling by the Wnt pathway has been shown, but how and which components of Wnt signaling are involved in the activation of Hippo signaling during nutrient starvation are unknown. Here, we report that a reduction in the level of low‐density lipoprotein receptor‐related protein 6 ( LRP 6) during nutrient starvation induces phosphorylation and cytoplasmic localization of YAP , inhibiting YAP ‐dependent transcription. Phosphorylation of YAP via loss of LRP 6 is mediated by large tumor suppressor kinases 1/2 ( LATS 1/2) and Merlin. We found that O ‐Glc NA cylation of LRP 6 was reduced, and the overall amount of LRP 6 was decreased via endocytosis‐mediated lysosomal degradation during nutrient starvation. Merlin binds to LRP 6; when LRP 6 is less O ‐Glc NA cylated, Merlin dissociates from it and becomes capable of interacting with LATS 1 to induce phosphorylation of YAP . Our data suggest that LRP 6 has unexpected roles as a nutrient sensor and Hippo signaling regulator.