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

Shin Morioka, Hiroki Nakanishi, Toshiyoshi Yamamoto, Junya Hasegawa, Emi Tokuda, Tomoya Hikita, Tomoko Sakihara, Yuuki Kugii, Chitose Oneyama, Masakazu Yamazaki, Akira Suzuki, Junko Sasaki () and Takehiko Sasaki ()
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Shin Morioka: Tokyo Medical and Dental University
Hiroki Nakanishi: Akita University
Toshiyoshi Yamamoto: Tokyo Medical and Dental University
Junya Hasegawa: Tokyo Medical and Dental University
Emi Tokuda: Tokyo Medical and Dental University
Tomoya Hikita: Aichi Cancer Center Research Institute, Chikusa-ku
Tomoko Sakihara: Tokyo Medical and Dental University
Yuuki Kugii: 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
Takehiko Sasaki: Tokyo Medical and Dental University

Nature Communications, 2022, vol. 13, issue 1, 1-9

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-021-27648-z

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