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A mass spectrometric method for in-depth profiling of phosphoinositide regioisomers and their disease-associated regulation

Author

Listed:
  • Shin Morioka

    (Tokyo Medical and Dental University
    Tokyo Medical and Dental University)

  • Hiroki Nakanishi

    (Akita University)

  • Toshiyoshi Yamamoto

    (Tokyo Medical and Dental University
    Tokyo Medical and Dental University)

  • Junya Hasegawa

    (Tokyo Medical and Dental University
    Tokyo Medical and Dental University)

  • Emi Tokuda

    (Tokyo Medical and Dental University
    Tokyo Medical and Dental University)

  • Tomoya Hikita

    (Aichi Cancer Center Research Institute, Chikusa-ku)

  • Tomoko Sakihara

    (Tokyo Medical and Dental University
    Tokyo Medical and Dental University)

  • Yuuki Kugii

    (Tokyo Medical and Dental University
    Tokyo Medical and Dental University)

  • Chitose Oneyama

    (Aichi Cancer Center Research Institute, Chikusa-ku)

  • Masakazu Yamazaki

    (Akita University Graduate School of Medicine)

  • Akira Suzuki

    (Kobe University)

  • Junko Sasaki

    (Tokyo Medical and Dental University
    Tokyo Medical and Dental University)

  • Takehiko Sasaki

    (Tokyo Medical and Dental University
    Tokyo Medical and Dental University)

Abstract

Phosphoinositides are a family of membrane lipids essential for many biological and pathological processes. Due to the existence of multiple phosphoinositide regioisomers and their low intracellular concentrations, profiling these lipids and linking a specific acyl variant to a change in biological state have been difficult. To enable the comprehensive analysis of phosphoinositide phosphorylation status and acyl chain identity, we develop PRMC-MS (Phosphoinositide Regioisomer Measurement by Chiral column chromatography and Mass Spectrometry). Using this method, we reveal a severe skewing in acyl chains in phosphoinositides in Pten-deficient prostate cancer tissues, extracellular mobilization of phosphoinositides upon expression of oncogenic PIK3CA, and a unique profile for exosomal phosphoinositides. Thus, our approach allows characterizing the dynamics of phosphoinositide acyl variants in intracellular and extracellular milieus.

Suggested Citation

  • Shin Morioka & Hiroki Nakanishi & Toshiyoshi Yamamoto & Junya Hasegawa & Emi Tokuda & Tomoya Hikita & Tomoko Sakihara & Yuuki Kugii & Chitose Oneyama & Masakazu Yamazaki & Akira Suzuki & Junko Sasaki , 2022. "A mass spectrometric method for in-depth profiling of phosphoinositide regioisomers and their disease-associated regulation," Nature Communications, Nature, vol. 13(1), pages 1-9, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-021-27648-z
    DOI: 10.1038/s41467-021-27648-z
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