A human phospholipid phosphatase activated by a transmembrane control module
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 el...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2012-11-01
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| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520412441 |
| _version_ | 1818735077314527232 |
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| author | Christian R. Halaszovich Michael G. Leitner Angeliki Mavrantoni Audrey Le Ludivine Frezza Anja Feuer Daniela N. Schreiber Carlos A. Villalba-Galea Dominik Oliver |
| author_facet | Christian R. Halaszovich Michael G. Leitner Angeliki Mavrantoni Audrey Le Ludivine Frezza Anja Feuer Daniela N. Schreiber Carlos A. Villalba-Galea Dominik Oliver |
| author_sort | Christian R. Halaszovich |
| collection | DOAJ |
| description | 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)P2. 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. |
| first_indexed | 2024-12-18T00:15:31Z |
| format | Article |
| id | doaj.art-b8403ec3445b4b2ca548629ef0b4fadb |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-18T00:15:31Z |
| publishDate | 2012-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-b8403ec3445b4b2ca548629ef0b4fadb2022-12-21T21:27:33ZengElsevierJournal of Lipid Research0022-22752012-11-01531122662274A human phospholipid phosphatase activated by a transmembrane control moduleChristian R. Halaszovich0Michael G. Leitner1Angeliki Mavrantoni2Audrey Le3Ludivine Frezza4Anja Feuer5Daniela N. Schreiber6Carlos A. Villalba-Galea7Dominik Oliver8Institute of Physiology and Pathophysiology, Philipps-Universität Marburg, 35037, Marburg, GermanyInstitute of Physiology and Pathophysiology, Philipps-Universität Marburg, 35037, Marburg, GermanyInstitute of Physiology and Pathophysiology, Philipps-Universität Marburg, 35037, Marburg, GermanyDepartment of Physiology and Biophysics, Virginia Commonwealth University, Richmond, VA 23298;Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, IL 60637Institute of Physiology and Pathophysiology, Philipps-Universität Marburg, 35037, Marburg, GermanyInstitute of Physiology and Pathophysiology, Philipps-Universität Marburg, 35037, Marburg, GermanyTo whom correspondence should be addressed.; Department of Physiology and Biophysics, Virginia Commonwealth University, Richmond, VA 23298;To whom correspondence should be addressed.; Institute of Physiology and Pathophysiology, Philipps-Universität Marburg, 35037, Marburg, GermanyIn 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)P2. 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.http://www.sciencedirect.com/science/article/pii/S0022227520412441phosphoinositidesvoltage sensorelectrochemical couplingion channellipid signaling |
| spellingShingle | Christian R. Halaszovich Michael G. Leitner Angeliki Mavrantoni Audrey Le Ludivine Frezza Anja Feuer Daniela N. Schreiber Carlos A. Villalba-Galea Dominik Oliver A human phospholipid phosphatase activated by a transmembrane control module Journal of Lipid Research phosphoinositides voltage sensor electrochemical coupling ion channel lipid signaling |
| title | A human phospholipid phosphatase activated by a transmembrane control module |
| title_full | A human phospholipid phosphatase activated by a transmembrane control module |
| title_fullStr | A human phospholipid phosphatase activated by a transmembrane control module |
| title_full_unstemmed | A human phospholipid phosphatase activated by a transmembrane control module |
| title_short | A human phospholipid phosphatase activated by a transmembrane control module |
| title_sort | human phospholipid phosphatase activated by a transmembrane control module |
| topic | phosphoinositides voltage sensor electrochemical coupling ion channel lipid signaling |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520412441 |
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