Endosomal phosphatidylserine is critical for the YAP signalling pathway in proliferating cells.

Nature Communications
Tatsuyuki MatsudairaTomohiko Taguchi

Abstract

Yes-associated protein (YAP) is a recently discovered growth-promoting transcription coactivator that has been shown to regulate the malignancy of various cancers. How YAP is regulated is not fully understood. Here, we show that one of the factors regulating YAP is phosphatidylserine (PS) in recycling endosomes (REs). We use proximity biotinylation to find proteins proximal to PS. Among these proteins are YAP and multiple proteins related to YAP signalling. Knockdown of ATP8A1 (an RE PS-flippase) or evectin-2 (an RE-resident protein) and masking of PS in the cytoplasmic leaflet of membranes, all suppress nuclear localization of YAP and YAP-dependent transcription. ATP8A1 knockdown increases the phosphorylated (activated) form of Lats1 that phosphorylates and inactivates YAP, whereas evectin-2 knockdown reduces the ubiquitination and increased the level of Lats1. The proliferation of YAP-dependent metastatic cancer cells is suppressed by knockdown of ATP8A1 or evectin-2. These results suggest a link between a membrane phospholipid and cell proliferation.

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Citations

Jun 21, 2019·Proceedings of the National Academy of Sciences of the United States of America·Takuma TsujiToyoshi Fujimoto
Aug 17, 2020·The Biochemical Journal·Walaa E Kattan, John F Hancock
Feb 6, 2020·Frontiers in Cell and Developmental Biology·Shilpi Verghese, Ken Moberg
Jan 25, 2019·Blood Advances·Weidong JingStefan Bröer
Oct 17, 2019·Cell Communication and Signaling : CCS·Jason G Kay, Gregory D Fairn
Jan 26, 2021·Frontiers in Cell and Developmental Biology·Giona Pedrioli, Paolo Paganetti
May 16, 2021·Proceedings of the National Academy of Sciences of the United States of America·Seunghyi KookSusan H Guttentag

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Methods Mentioned

BETA
nuclear translocation
GTPase
ubiquitination
PCR
immunoprecipitation

Software Mentioned

JACoP
ProteinPilot
ImageJ
RGB Profile Plot
BioID

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