title: Potential role of voltage-sensing phosphatases in regulation of cell structure through the production of PI(3,4)P2.
abstract: Voltage-sensing phosphatase, VSP, consists of the transmembrane domain, operating as the voltage sensor, and the cytoplasmic domain with phosphoinositide-phosphatase activities. The voltage sensor tightly couples with the cytoplasmic phosphatase and membrane depolarization induces dephosphorylation of several species of phosphoinositides. VSP gene is conserved from urochordate to human. There are some diversities among VSP ortholog proteins; range of voltage of voltage sensor motions as well as substrate selectivity. In contrast with recent understandings of biophysical mechanisms of VSPs, little is known about its physiological roles. Here we report that chick ortholog of VSP (designated as Gg-VSP) induces morphological feature of cell process outgrowths with round cell body in DF-1 fibroblasts upon its forced expression. Expression of the voltage sensor mutant, Gg-VSPR153Q with shifted voltage dependence to a lower voltage led to more frequent changes of cell morphology than the wild-type protein. Coexpression of PTEN that dephosphorylates PI(3,4)P2 suppressed this effect by Gg-VSP, indicating that the increase of PI(3,4)P2 leads to changes of cell shape. In addition, visualization of PI(3,4)P2 with the fluorescent protein fused with the TAPP1-derived pleckstrin homology (PH) domain suggested that Gg-VSP influenced the distribution of PI(3,4)P2 . These findings raise a possibility that one of the VSP's functions could be to regulate cell morphology through voltage-sensitive tuning of phosphoinositide profile.
authors.affiliation: Faculty of Pharmaceutical Sciences, Department of Life and Health Sciences, Teikyo University, Tokyo, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Yamaguchi
authors.forename: Tatsuki
authors.initials: T
authors.lastname: Kurokawa
authors.forename: Ikuko
authors.initials: I
authors.lastname: Taira
authors.forename: Naoya
authors.initials: N
authors.lastname: Aoki
authors.forename: Souhei
authors.initials: S
authors.lastname: Sakata
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Okamura
authors.forename: Koichi J
authors.initials: KJ
authors.lastname: Homma
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D048430:Cell Shape / Q000502:physiology; D002645:Chickens; D003001:Cloning, Molecular; D005347:Fibroblasts / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D006801:Humans; D008564:Membrane Potentials / Q000502:physiology*; D010716:Phosphatidylinositols / Q000096:biosynthesis*; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*
chemical_list: D010716:Phosphatidylinositols; C118301:phosphoinositide-3,4-bisphosphate; D010744:Phosphoric Monoester Hydrolases