Masato Yasui, Satomi Matsuoka, Masahiro Ueda (2014) PTEN hopping on the cell membrane is regulated via a positively-charged C2 domain., PLoS computational biology, Volume 10, Number 9, pp. e1003817
Published in 2014 Sep (Electronic publication in Sept. 11, 2014, midnight )
(Abstract) PTEN, a tumor suppressor that is frequently mutated in a wide spectrum of cancers, exerts PI(3,4,5)P3 phosphatase activities that are regulated by its dynamic shuttling between the membrane and cytoplasm. Direct observation of PTEN in the interfacial environment can offer quantitative information about the shuttling dynamics, but remains elusive. Here we show that positively charged residues located in the calpha2 helix of the C2 domain are necessary for the membrane localization of PTEN via stable electrostatic interactions in Dictyostelium discoideum. Single-molecule imaging analyses revealed that PTEN molecules moved distances much larger than expected had they been caused by lateral diffusion, a phenomenon we call "hopping." Our novel single-particle tracking analysis method found that the calpha2 helix aids in regulating the hopping and stable-binding states. The dynamically established membrane localization of PTEN was revealed to be essential for developmental processes and clarified a fundamental regulation mechanism of the protein quantity and activity on the plasma membrane.(MeSH Terms)