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J Lipid Res
2012 Nov 01;5311:2266-74. doi: 10.1194/jlr.M026021.
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A human phospholipid phosphatase activated by a transmembrane control module.
Halaszovich CR
,
Leitner MG
,
Mavrantoni A
,
Le A
,
Frezza L
,
Feuer A
,
Schreiber DN
,
Villalba-Galea CA
,
Oliver D
.
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In voltage-sensitive phosphatases (VSPs), a transmembrane voltage sensor domain (VSD) controls an intracellular phosphoinositide phosphatase domain, thereby enabling immediate initiation of intracellular signals by membrane depolarization. The existence of such a mechanism in mammals has remained elusive, despite the presence of VSP-homologous proteins in mammalian cells, in particular in sperm precursor cells. Here we demonstrate activation of a human VSP (hVSP1/TPIP) by an intramolecular switch. By engineering a chimeric hVSP1 with enhanced plasma membrane targeting containing the VSD of a prototypic invertebrate VSP, we show that hVSP1 is a phosphoinositide-5-phosphatase whose predominant substrate is PI(4,5)P(2). In the chimera, enzymatic activity is controlled by membrane potential via hVSP1's endogenous phosphoinositide binding motif. These findings suggest that the endogenous VSD of hVSP1 is a control module that initiates signaling through the phosphatase domain and indicate a role for VSP-mediated phosphoinositide signaling in mammals.
Di Paolo,
Phosphoinositides in cell regulation and membrane dynamics.
2006, Pubmed
Di Paolo,
Phosphoinositides in cell regulation and membrane dynamics.
2006,
Pubmed
Falkenburger,
Kinetics of PIP2 metabolism and KCNQ2/3 channel regulation studied with a voltage-sensitive phosphatase in living cells.
2010,
Pubmed
Guipponi,
The murine orthologue of the Golgi-localized TPTE protein provides clues to the evolutionary history of the human TPTE gene family.
2001,
Pubmed
Halaszovich,
Ci-VSP is a depolarization-activated phosphatidylinositol-4,5-bisphosphate and phosphatidylinositol-3,4,5-trisphosphate 5'-phosphatase.
2009,
Pubmed
Hobiger,
Coupling of Ci-VSP modules requires a combination of structure and electrostatics within the linker.
2012,
Pubmed
,
Xenbase
Hossain,
Enzyme domain affects the movement of the voltage sensor in ascidian and zebrafish voltage-sensing phosphatases.
2008,
Pubmed
,
Xenbase
Inoue,
An inducible translocation strategy to rapidly activate and inhibit small GTPase signaling pathways.
2005,
Pubmed
Iwasaki,
A voltage-sensing phosphatase, Ci-VSP, which shares sequence identity with PTEN, dephosphorylates phosphatidylinositol 4,5-bisphosphate.
2008,
Pubmed
,
Xenbase
Jain,
Infrastructure for the life sciences: design and implementation of the UniProt website.
2009,
Pubmed
Kohout,
Subunit organization and functional transitions in Ci-VSP.
2008,
Pubmed
Kohout,
Electrochemical coupling in the voltage-dependent phosphatase Ci-VSP.
2010,
Pubmed
Kurokawa,
3' Phosphatase activity toward phosphatidylinositol 3,4-bisphosphate [PI(3,4)P2] by voltage-sensing phosphatase (VSP).
2012,
Pubmed
Lacroix,
Controlling the activity of a phosphatase and tensin homolog (PTEN) by membrane potential.
2011,
Pubmed
,
Xenbase
Leslie,
PTEN: The down side of PI 3-kinase signalling.
2002,
Pubmed
Leslie,
PtdIns(3,4,5)P(3)-dependent and -independent roles for PTEN in the control of cell migration.
2007,
Pubmed
Lindner,
Probing the regulation of TASK potassium channels by PI4,5P₂ with switchable phosphoinositide phosphatases.
2011,
Pubmed
Liu,
A glutamate switch controls voltage-sensitive phosphatase function.
2012,
Pubmed
Maehama,
PTEN and myotubularin: novel phosphoinositide phosphatases.
2001,
Pubmed
Matsuda,
Crystal structure of the cytoplasmic phosphatase and tensin homolog (PTEN)-like region of Ciona intestinalis voltage-sensing phosphatase provides insight into substrate specificity and redox regulation of the phosphoinositide phosphatase activity.
2011,
Pubmed
Mayinger,
Regulation of Golgi function via phosphoinositide lipids.
2009,
Pubmed
Murata,
Phosphoinositide phosphatase activity coupled to an intrinsic voltage sensor.
2005,
Pubmed
,
Xenbase
Murata,
Depolarization activates the phosphoinositide phosphatase Ci-VSP, as detected in Xenopus oocytes coexpressing sensors of PIP2.
2007,
Pubmed
,
Xenbase
Neuhaus,
Kidney specific expression of cTPTE during development of the chick embryo.
2009,
Pubmed
Ogasawara,
Gene expression profile of Ci-VSP in juveniles and adult blood cells of ascidian.
2011,
Pubmed
Pirruccello,
Inositol 5-phosphatases: insights from the Lowe syndrome protein OCRL.
2012,
Pubmed
Ratzan,
Voltage sensitive phosphoinositide phosphatases of Xenopus: their tissue distribution and voltage dependence.
2011,
Pubmed
,
Xenbase
Reymond,
Human chromosome 21 gene expression atlas in the mouse.
2002,
Pubmed
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
Sutton,
Evolution of the voltage sensor domain of the voltage-sensitive phosphoinositide phosphatase VSP/TPTE suggests a role as a proton channel in eutherian mammals.
2012,
Pubmed
Tapparel,
The TPTE gene family: cellular expression, subcellular localization and alternative splicing.
2003,
Pubmed
Várnai,
Live cell imaging of phosphoinositide dynamics with fluorescent protein domains.
2006,
Pubmed
Villalba-Galea,
Coupling between the voltage-sensing and phosphatase domains of Ci-VSP.
2009,
Pubmed
,
Xenbase
Villalba-Galea,
S4-based voltage sensors have three major conformations.
2008,
Pubmed
Walker,
TPIP: a novel phosphoinositide 3-phosphatase.
2001,
Pubmed
Watt,
Subcellular localization of phosphatidylinositol 4,5-bisphosphate using the pleckstrin homology domain of phospholipase C delta1.
2002,
Pubmed
Wu,
PTEN 2, a Golgi-associated testis-specific homologue of the PTEN tumor suppressor lipid phosphatase.
2001,
Pubmed
