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

Tatsuyuki Matsudaira, Kojiro Mukai, Taishin Noguchi, Junya Hasegawa, Tomohisa Hatta, Shun Ichiro Iemura, Tohru Natsume, Norio Miyamura, Hiroshi Nishina, Jun Nakayama, Kentaro Senba, Takuya Tomita, Shigeo Murata, Hiroyuki Arai, Tomohiko Taguchi

    Research output: Contribution to journalArticle

    5 Citations (Scopus)

    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.

    Original languageEnglish
    Article number1246
    JournalNature Communications
    Volume8
    Issue number1
    DOIs
    Publication statusPublished - 2017 Dec 1

    Fingerprint

    Phosphatidylserines
    proteins
    Proteins
    Endosomes
    recycling
    Recycling
    Transcription
    cancer
    membranes
    Biotinylation
    Membranes
    Neoplasms
    Ubiquitination
    Cell proliferation
    masking
    proximity
    Phospholipids
    Cells
    Cell Proliferation
    Cell Membrane

    ASJC Scopus subject areas

    • Chemistry(all)
    • Biochemistry, Genetics and Molecular Biology(all)
    • Physics and Astronomy(all)

    Cite this

    Matsudaira, T., Mukai, K., Noguchi, T., Hasegawa, J., Hatta, T., Iemura, S. I., ... Taguchi, T. (2017). Endosomal phosphatidylserine is critical for the YAP signalling pathway in proliferating cells. Nature Communications, 8(1), [1246]. https://doi.org/10.1038/s41467-017-01255-3

    Endosomal phosphatidylserine is critical for the YAP signalling pathway in proliferating cells. / Matsudaira, Tatsuyuki; Mukai, Kojiro; Noguchi, Taishin; Hasegawa, Junya; Hatta, Tomohisa; Iemura, Shun Ichiro; Natsume, Tohru; Miyamura, Norio; Nishina, Hiroshi; Nakayama, Jun; Senba, Kentaro; Tomita, Takuya; Murata, Shigeo; Arai, Hiroyuki; Taguchi, Tomohiko.

    In: Nature Communications, Vol. 8, No. 1, 1246, 01.12.2017.

    Research output: Contribution to journalArticle

    Matsudaira, T, Mukai, K, Noguchi, T, Hasegawa, J, Hatta, T, Iemura, SI, Natsume, T, Miyamura, N, Nishina, H, Nakayama, J, Senba, K, Tomita, T, Murata, S, Arai, H & Taguchi, T 2017, 'Endosomal phosphatidylserine is critical for the YAP signalling pathway in proliferating cells', Nature Communications, vol. 8, no. 1, 1246. https://doi.org/10.1038/s41467-017-01255-3
    Matsudaira, Tatsuyuki ; Mukai, Kojiro ; Noguchi, Taishin ; Hasegawa, Junya ; Hatta, Tomohisa ; Iemura, Shun Ichiro ; Natsume, Tohru ; Miyamura, Norio ; Nishina, Hiroshi ; Nakayama, Jun ; Senba, Kentaro ; Tomita, Takuya ; Murata, Shigeo ; Arai, Hiroyuki ; Taguchi, Tomohiko. / Endosomal phosphatidylserine is critical for the YAP signalling pathway in proliferating cells. In: Nature Communications. 2017 ; Vol. 8, No. 1.
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