Single-Cell Biophysics: Measurement, Modulation, and Modeling

Single-Cell Biophysics: Measurement, Modulation, and Modeling

Poster Abstracts

63-POS Board 32 Mutual Inhibition between PTEN and PIP3 Regulates Excitability for Eukaryotic Chemotaxis Satomi Matsuoka 1,2 , Masahiro Ueda 2,1 . 1 RIKEN Quantitative Biology Center, Osaka, Japan, 2 Osaka University, Osaka, Japan. Excitable signal transduction in eukaryotic chemotaxis generates PI(3,4,5)P3-enriched domain asymmetrically on the cell membrane that serves as an all-or-none signal for cell migration. Here we report that PTEN, a PI(3,4,5)P3 phosphatase, regulates the excitability by constituting the mutual inhibition relationship with PI(3,4,5)P3. PTEN suppresses PI(3,4,5)P3 at the sub- threshold level by the phosphatase activity but is excluded from the membrane by PI(3,4,5)P3 at the supra-threshold level ensuring the PI(3,4,5)P3 excitation. We further demonstrates with single-molecule resolution that a subpopulation of PTEN adopting the stably-binding state with longer membrane-binding lifetimes acts as a regulatory point of the mutual inhibition as well as chemoattractant stimuli, thereby facilitating the PI(3,4,5)P3 excitation via the exclusion along the gradients. These observations illustrate multistate transitions of PTEN and the positive feedback regulations as mechanisms to regulate excitability in the cellular decision-making for chemotaxis and also suggest important implications in the tumor suppression.

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