Satoshi Kofuji, Kara Wolfe, Kazutaka Sumita, Shun Kageyama, Hirofumi Yoshino, Yoshihisa Hirota, Aki Ogawa-Iio, Hirotaka Kanoh, Mika Sasaki, Kaori Kofuji, Mindy I Davis, Rajan Pragani, Min Shen, Matthew B Boxer, Fubito Nakatsu, Kiyomi Nigorikawa, Takehiko Sasaki, Koh Takeuchi, Toshiya Senda, Seong M Kim, Aimee L Edinger, Anton Simeonov, Atsuo T Sasaki
In animal cells, vacuoles are absent, but can be induced by diseases and drugs. While phosphoinositides are critical for membrane trafficking, their role in the formation of these vacuoles remains unclear. The immunosuppressive KRP203/Mocravimod, which antagonizes sphingosine-1-phosphate receptors, has been identified as having novel multimodal activity against phosphoinositide kinases. However, the impact of this novel KRP203 activity is unknown. Here, we show that KRP203 disrupts the spatial organization of phosphoinositides and induces extensive vacuolization in tumor cells and immortalized fibroblasts...
April 27, 2024: Biochemical and Biophysical Research Communications