ORCiD
0000-0002-6489-4651
Document Type
Article
Publication Title
Journal of Lipid Research
ISSN
1539-7262
Volume
53
Issue
11
DOI
10.1194/jlr.M026021
First Page
2266
Last Page
2274
Publication Date
11-1-2012
Abstract
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.
Recommended Citation
Halaszovich, C. R.,
Leitner, M. G.,
Mavrantoni, A.,
Le, A.,
Frezza, L.,
Feuer, A.,
Schreiber, D. N.,
Villalba-Galea, C. A.,
&
Oliver, D.
(2012).
A human phospholipid phosphatase activated by a transmembrane control module.
Journal of Lipid Research, 53(11), 2266–2274.
DOI: 10.1194/jlr.M026021
https://scholarlycommons.pacific.edu/phs-facarticles/312
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