title: Asymmetries in H+/K+-ATPase and cell membrane potentials comprise a very early step in left-right patterning.
abstract: A pharmacological screen identified the H+ and K+ ATPase transporter as obligatory for normal orientation of the left-right body axis in Xenopus. Maternal H+/K+-ATPase mRNA is symmetrically expressed in the 1-cell Xenopus embryo but becomes localized during the first two cell divisions, demonstrating that asymmetry is generated within two hours postfertilization. Although H+/K+-ATPase subunit mRNAs are symmetrically localized in chick embryos, an endogenous H+/K+-ATPase-dependent difference in membrane voltage potential exists between the left and right sides of the primitive streak. In both species, pharmacologic or genetic perturbation of endogenous H+/K+-ATPase randomized the sided pattern of asymmetrically expressed genes and induced organ heterotaxia. Thus, LR asymmetry determination depends on a very early differential ion flux created by H+/K+-ATPase activity.
authors.affiliation: Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Levin
authors.forename: Thorleif
authors.initials: T
authors.lastname: Thorlin
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Robinson
authors.forename: Taisaku
authors.initials: T
authors.lastname: Nogi
authors.forename: Mark
authors.initials: M
authors.lastname: Mercola
mesh_terms: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000818:Animals; D017609:Barium Compounds / Q000494:pharmacology; D019521:Body Patterning; D002462:Cell Membrane / Q000378:metabolism*; D002642:Chick Embryo; D002712:Chlorides / Q000494:pharmacology; D004594:Electrophysiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D017506:H(+)-K(+)-Exchanging ATPase / Q000737:chemistry* / Q000378:metabolism*; D017403:In Situ Hybridization; D064747:Lansoprazole; D008564:Membrane Potentials; D008969:Molecular Sequence Data; D009853:Omeprazole / Q000031:analogs & derivatives* / Q000494:pharmacology; D024661:Potassium Channels, Inwardly Rectifying / Q000378:metabolism; D054328:Proton Pump Inhibitors; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors; D014981:Xenopus
chemical_list: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D017609:Barium Compounds; D002712:Chlorides; D004791:Enzyme Inhibitors; D024661:Potassium Channels, Inwardly Rectifying; D054328:Proton Pump Inhibitors; D012333:RNA, Messenger; D064747:Lansoprazole; C024986:barium chloride; D017506:H(+)-K(+)-Exchanging ATPase; D009853:Omeprazole