Tumor suppressor PTEN acts through dynamic interaction with the plasma membrane

Francisca Vazquez, Satomi Matsuoka, William R. Sellers, Toshio Yanagida, Masahiro Ueda, Peter N. Devreotes

Research output: Contribution to journalArticlepeer-review

Abstract

The tumor suppressor function of PTEN is strongly linked to its ability to dephosphorylate phosphatidylinositol-3,4,5 trisphosphate and, thereby, control cell growth, survival, and migration. However, the mechanism of action of PTEN in living cells is largely unexplored. Here we use single-molecule TIRF microscopy in living cells to reveal that the enzyme binds to the membrane for a few hundred milliseconds, sufficient to degrade several phosphatidylinositol-3, 4,5 trisphosphate molecules. Deletion of an N-terminal lipid-binding motif completely abrogates membrane interaction and in vivo function. Several mechanisms, including C-terminal tail phosphorylations, appear to hold PTEN in a constrained conformation that limits its rate of association with the membrane. The steady-state level of bound PTEN is highest at sites of retracting membrane, including the rear of highly polarized cells. The dynamic membrane association could be modulated temporally or spatially to alter PTEN activity in specific physiological situations and could have important implications for tumor suppressor function.

Original languageEnglish (US)
Pages (from-to)3633-3638
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume103
Issue number10
DOIs
StatePublished - Mar 7 2006

Keywords

  • Membrane binding
  • Single molecule

ASJC Scopus subject areas

  • General

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