Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
J Biol Chem
2011 May 20;28620:17945-53. doi: 10.1074/jbc.M110.201749.
Show Gene links
Show Anatomy links
Controlling the activity of a phosphatase and tensin homolog (PTEN) by membrane potential.
Lacroix J
,
Halaszovich CR
,
Schreiber DN
,
Leitner MG
,
Bezanilla F
,
Oliver D
,
Villalba-Galea CA
.
???displayArticle.abstract???
The recently discovered voltage-sensitive phosphatases (VSPs) hydrolyze phosphoinositides upon depolarization of the membrane potential, thus representing a novel principle for the transduction of electrical activity into biochemical signals. Here, we demonstrate the possibility to confer voltage sensitivity to cytosolic enzymes. By fusing the tumor suppressor PTEN to the voltage sensor of the prototypic VSP from Ciona intestinalis, Ci-VSP, we generated chimeric proteins that are voltage-sensitive and display PTEN-like enzymatic activity in a strictly depolarization-dependent manner in vivo. Functional coupling of the exogenous enzymatic activity to the voltage sensor is mediated by a phospholipid-binding motif at the interface between voltage sensor and catalytic domains. Our findings reveal that the main domains of VSPs and related phosphoinositide phosphatases are intrinsically modular and define structural requirements for coupling of enzymatic activity to a voltage sensor domain. A key feature of this prototype of novel engineered voltage-sensitive enzymes, termed Ci-VSPTEN, is the novel ability to switch enzymatic activity of PTEN rapidly and reversibly. We demonstrate that experimental control of Ci-VSPTEN can be obtained either by electrophysiological techniques or more general techniques, using potassium-induced depolarization of intact cells. Thus, Ci-VSPTEN provides a novel approach for studying the complex mechanism of activation, cellular control, and pharmacology of this important tumor suppressor. Moreover, by inducing temporally precise perturbation of phosphoinositide concentrations, Ci-VSPTEN will be useful for probing the role and specificity of these messengers in many cellular processes and to analyze the timing of phosphoinositide signaling.
Balla,
A plasma membrane pool of phosphatidylinositol 4-phosphate is generated by phosphatidylinositol 4-kinase type-III alpha: studies with the PH domains of the oxysterol binding protein and FAPP1.
2005, Pubmed
Balla,
A plasma membrane pool of phosphatidylinositol 4-phosphate is generated by phosphatidylinositol 4-kinase type-III alpha: studies with the PH domains of the oxysterol binding protein and FAPP1.
2005,
Pubmed
Campbell,
Allosteric activation of PTEN phosphatase by phosphatidylinositol 4,5-bisphosphate.
2003,
Pubmed
Cha,
Fluorescence techniques for studying cloned channels and transporters expressed in Xenopus oocytes.
1998,
Pubmed
,
Xenbase
Chen,
Inhibition of a background potassium channel by Gq protein alpha-subunits.
2006,
Pubmed
Cremona,
Essential role of phosphoinositide metabolism in synaptic vesicle recycling.
1999,
Pubmed
Das,
Membrane-binding and activation mechanism of PTEN.
2003,
Pubmed
Denning,
A short N-terminal sequence of PTEN controls cytoplasmic localization and is required for suppression of cell growth.
2007,
Pubmed
Falkenburger,
Kinetics of PIP2 metabolism and KCNQ2/3 channel regulation studied with a voltage-sensitive phosphatase in living cells.
2010,
Pubmed
Finkbeiner,
Ca2+ channel-regulated neuronal gene expression.
1998,
Pubmed
Halaszovich,
Ci-VSP is a depolarization-activated phosphatidylinositol-4,5-bisphosphate and phosphatidylinositol-3,4,5-trisphosphate 5'-phosphatase.
2009,
Pubmed
Haucke,
Phosphoinositide regulation of clathrin-mediated endocytosis.
2005,
Pubmed
Hossain,
Enzyme domain affects the movement of the voltage sensor in ascidian and zebrafish voltage-sensing phosphatases.
2008,
Pubmed
,
Xenbase
Iwasaki,
A voltage-sensing phosphatase, Ci-VSP, which shares sequence identity with PTEN, dephosphorylates phosphatidylinositol 4,5-bisphosphate.
2008,
Pubmed
,
Xenbase
Kimber,
Evidence that the tandem-pleckstrin-homology-domain-containing protein TAPP1 interacts with Ptd(3,4)P2 and the multi-PDZ-domain-containing protein MUPP1 in vivo.
2002,
Pubmed
Kingsbury,
Calcineurin activity is required for depolarization-induced, CREB-dependent gene transcription in cortical neurons.
2007,
Pubmed
Kohout,
Subunit organization and functional transitions in Ci-VSP.
2008,
Pubmed
Kohout,
Electrochemical coupling in the voltage-dependent phosphatase Ci-VSP.
2010,
Pubmed
Lambert,
ESyPred3D: Prediction of proteins 3D structures.
2002,
Pubmed
Lee,
Crystal structure of the PTEN tumor suppressor: implications for its phosphoinositide phosphatase activity and membrane association.
1999,
Pubmed
,
Xenbase
Lee,
Reversible inactivation of the tumor suppressor PTEN by H2O2.
2002,
Pubmed
Leslie,
Understanding PTEN regulation: PIP2, polarity and protein stability.
2008,
Pubmed
Leslie,
PTEN: The down side of PI 3-kinase signalling.
2002,
Pubmed
Liu,
Phosphoinositide phosphatases in cell biology and disease.
2010,
Pubmed
Maehama,
The tumor suppressor, PTEN/MMAC1, dephosphorylates the lipid second messenger, phosphatidylinositol 3,4,5-trisphosphate.
1998,
Pubmed
Milosevic,
Plasmalemmal phosphatidylinositol-4,5-bisphosphate level regulates the releasable vesicle pool size in chromaffin cells.
2005,
Pubmed
Murata,
Depolarization activates the phosphoinositide phosphatase Ci-VSP, as detected in Xenopus oocytes coexpressing sensors of PIP2.
2007,
Pubmed
,
Xenbase
Murata,
Phosphoinositide phosphatase activity coupled to an intrinsic voltage sensor.
2005,
Pubmed
,
Xenbase
Ooms,
The role of the inositol polyphosphate 5-phosphatases in cellular function and human disease.
2009,
Pubmed
Pagliarini,
A PTEN-like phosphatase with a novel substrate specificity.
2004,
Pubmed
Rahdar,
A phosphorylation-dependent intramolecular interaction regulates the membrane association and activity of the tumor suppressor PTEN.
2009,
Pubmed
Redfern,
PTEN phosphatase selectively binds phosphoinositides and undergoes structural changes.
2008,
Pubmed
Schaechinger,
Nonmammalian orthologs of prestin (SLC26A5) are electrogenic divalent/chloride anion exchangers.
2007,
Pubmed
Steck,
Identification of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers.
1997,
Pubmed
Stefani,
Cut-open oocyte voltage-clamp technique.
1998,
Pubmed
,
Xenbase
Suh,
Rapid chemically induced changes of PtdIns(4,5)P2 gate KCNQ ion channels.
2006,
Pubmed
Suh,
PIP2 is a necessary cofactor for ion channel function: how and why?
2008,
Pubmed
Tapparel,
The TPTE gene family: cellular expression, subcellular localization and alternative splicing.
2003,
Pubmed
Van der Kaay,
Distinct phosphatidylinositol 3-kinase lipid products accumulate upon oxidative and osmotic stress and lead to different cellular responses.
1999,
Pubmed
Varnai,
Rapidly inducible changes in phosphatidylinositol 4,5-bisphosphate levels influence multiple regulatory functions of the lipid in intact living cells.
2006,
Pubmed
Vazquez,
Tumor suppressor PTEN acts through dynamic interaction with the plasma membrane.
2006,
Pubmed
Villalba-Galea,
S4-based voltage sensors have three major conformations.
2008,
Pubmed
Villalba-Galea,
Coupling between the voltage-sensing and phosphatase domains of Ci-VSP.
2009,
Pubmed
,
Xenbase
Várnai,
Visualization of phosphoinositides that bind pleckstrin homology domains: calcium- and agonist-induced dynamic changes and relationship to myo-[3H]inositol-labeled phosphoinositide pools.
1998,
Pubmed
Walker,
TPIP: a novel phosphoinositide 3-phosphatase.
2001,
Pubmed
Walker,
The tumour-suppressor function of PTEN requires an N-terminal lipid-binding motif.
2004,
Pubmed
Wang,
Critical role of PIP5KI{gamma}87 in InsP3-mediated Ca(2+) signaling.
2004,
Pubmed
Wheeler,
CaMKII locally encodes L-type channel activity to signal to nuclear CREB in excitation-transcription coupling.
2008,
Pubmed
Wymann,
Lipid signalling in disease.
2008,
Pubmed
