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

Author

Listed:
  • Tatsuyuki Matsudaira

    (University of Tokyo)

  • Kojiro Mukai

    (University of Tokyo)

  • Taishin Noguchi

    (University of Tokyo)

  • Junya Hasegawa

    (University of Tokyo)

  • Tomohisa Hatta

    (National Institute of Advanced Industrial Science and Technology)

  • Shun-ichiro Iemura

    (Fukushima Medical University)

  • Tohru Natsume

    (National Institute of Advanced Industrial Science and Technology)

  • Norio Miyamura

    (Tokyo Medical and Dental University)

  • Hiroshi Nishina

    (Tokyo Medical and Dental University)

  • Jun Nakayama

    (Waseda University)

  • Kentaro Semba

    (Waseda University)

  • Takuya Tomita

    (The University of Tokyo)

  • Shigeo Murata

    (The University of Tokyo)

  • Hiroyuki Arai

    (University of Tokyo
    The University of Tokyo
    AMED-CREST, Japan Agency for Medical Research and Development)

  • Tomohiko Taguchi

    (University of Tokyo
    The University of Tokyo)

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.

Suggested Citation

  • Tatsuyuki Matsudaira & Kojiro Mukai & Taishin Noguchi & Junya Hasegawa & Tomohisa Hatta & Shun-ichiro Iemura & Tohru Natsume & Norio Miyamura & Hiroshi Nishina & Jun Nakayama & Kentaro Semba & Takuya , 2017. "Endosomal phosphatidylserine is critical for the YAP signalling pathway in proliferating cells," Nature Communications, Nature, vol. 8(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-01255-3
    DOI: 10.1038/s41467-017-01255-3
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