title: A calcineurin homologous protein is required for sodium-proton exchange events in the C. elegans intestine.
abstract: Caenorhabditis elegans defecation is a rhythmic behavior, composed of three sequential muscle contractions, with a 50-s periodicity. The motor program is driven by oscillatory calcium signaling in the intestine. Proton fluxes, which require sodium-proton exchangers at the apical and basolateral intestinal membranes, parallel the intestinal calcium flux. These proton shifts are critical for defecation-associated muscle contraction, nutrient uptake, and longevity. How sodium-proton exchangers are activated in time with intestinal calcium oscillation is not known. The posterior body defecation contraction mutant (pbo-1) encodes a calcium-binding protein with homology to calcineurin homologous proteins, which are putative cofactors for mammalian sodium-proton exchangers. Loss of pbo-1 function results in a weakened defecation muscle contraction and a caloric restriction phenotype. Both of these phenotypes also arise from dysfunctions in pH regulation due to mutations in intestinal sodium-proton exchangers. Dynamic, in vivo imaging of intestinal proton flux in pbo-1 mutants using genetically encoded pH biosensors demonstrates that proton movements associated with these sodium-proton exchangers are significantly reduced. The basolateral acidification that signals the first defecation motor contraction is scant in the mutant compared with a normal animal. Luminal and cytoplasmic pH shifts are much reduced in the absence of PBO-1 compared with control animals. We conclude that pbo-1 is required for normal sodium-proton exchanger activity and may couple calcium and proton signaling events.
authors.affiliation: Dept. of Biology, Oberlin College, Oberlin, OH 44074, USA.
authors.forename: Jamie
authors.initials: J
authors.lastname: Wagner
authors.forename: Erik
authors.initials: E
authors.lastname: Allman
authors.forename: Ashley
authors.initials: A
authors.lastname: Taylor
authors.forename: Kiri
authors.initials: K
authors.lastname: Ulmschneider
authors.forename: Timothy
authors.initials: T
authors.lastname: Kovanda
authors.forename: Bryne
authors.initials: B
authors.lastname: Ulmschneider
authors.forename: Keith
authors.initials: K
authors.lastname: Nehrke
authors.forename: Maureen A
authors.initials: MA
authors.lastname: Peters
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D019703:Calcineurin / Q000235:genetics / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D003672:Defecation / Q000502:physiology*; D007422:Intestines / Q000502:physiology*; D009119:Muscle Contraction / Q000502:physiology*; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D017923:Sodium-Hydrogen Exchangers / Q000235:genetics / Q000378:metabolism*
chemical_list: D029742:Caenorhabditis elegans Proteins; C569328:PBO-1 protein, C elegans; D017923:Sodium-Hydrogen Exchangers; D019703:Calcineurin; D002118:Calcium