A human phospholipid phosphatase activated by a transmembrane control module

摘要: In voltage-sensitive phosphatases (VSPs), a transmembrane voltage sensor domain (VSD) controls an intracellular phosphoinositide phosphatase domain, thereby enabling immediate initiation of signals by membrane depolarization. The existence such mechanism in mammals has remained elusive, despite the presence VSP-homologous proteins mammalian cells, particular sperm precursor cells. Here we demonstrate activation human VSP (hVSP1/TPIP) intramolecular switch. By engineering chimeric hVSP1 with enhanced plasma targeting containing VSD prototypic invertebrate VSP, show that is phosphoinositide-5-phosphatase whose predominant substrate PI(4,5)P2. chimera, enzymatic activity controlled potential via hVSP1’s endogenous binding motif. These findings suggest control module initiates signaling through and indicate role for VSP-mediated mammals.