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

RIKEN Quantitative Biology Center, Osaka, Japan,

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.