title: Zebrafish (Danio rerio) endomembrane antiporter similar to a yeast cation/H(+) transporter is required for neural crest development.
abstract: CAtion/H(+) eXchangers (CAXs) are integral membrane proteins that transport Ca(2+) or other cations by exchange with protons. While several yeast and plant CAX proteins have been characterized, no functional analysis of a vertebrate CAX homologue has yet been reported. In this study, we further characterize a CAX from yeast, VNX1, and initiate characterization of a zebrafish CAX (Cax1). Localization studies indicated that both Vnx1 and Cax1 proteins are found in endomembrane compartments. Biochemical characterization of endomembrane fractions from vnx1 mutant cells and zebrafish Cax1-expressing yeast cells suggested that both yeast and fish CAXs have Ca(2+)/H(+) antiport activities. Additionally, the vnx1 mutation was associated with heightened pH-sensitivity. In zebrafish embryos, cax1 was specifically expressed in neural crest cells. Morpholino knockdown of cax1 caused defects in neural crest development, including alterations in pigmentation, defects in jaw development, and reduction in expression of the neural crest marker, Pax7. Collectively, our findings provide insights into Vnx1 function and support an unexpected role of CAX transporters in animal growth and development.
authors.affiliation: Vegetable and Fruit Improvement Center, Texas A&M University, College Station, Texas 77845, USA.
authors.forename: Murli
authors.initials: M
authors.lastname: Manohar
authors.forename: Hui
authors.initials: H
authors.lastname: Mei
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Franklin
authors.forename: Elly M
authors.initials: EM
authors.lastname: Sweet
authors.forename: Toshiro
authors.initials: T
authors.lastname: Shigaki
authors.forename: Bruce B
authors.initials: BB
authors.lastname: Riley
authors.forename: Colin W
authors.initials: CW
authors.lastname: Macdiarmid
authors.forename: Kendal
authors.initials: K
authors.lastname: Hirschi
mesh_terms: D000818:Animals; D017920:Antiporters / Q000502:physiology*; D027682:Cation Transport Proteins; D004625:Embryo, Nonmammalian / Q000737:chemistry; D005656:Fungal Proteins; D006863:Hydrogen-Ion Concentration; D007425:Intracellular Membranes / Q000737:chemistry; D026901:Membrane Transport Proteins / Q000502:physiology; D009432:Neural Crest / Q000254:growth & development*; D029701:Saccharomyces cerevisiae Proteins; D017923:Sodium-Hydrogen Exchangers; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000502:physiology*
chemical_list: D017920:Antiporters; C551890:CAX1 protein, zebrafish; D027682:Cation Transport Proteins; D005656:Fungal Proteins; D026901:Membrane Transport Proteins; D029701:Saccharomyces cerevisiae Proteins; D017923:Sodium-Hydrogen Exchangers; C523520:Vnx1 protein, S cerevisiae; D029961:Zebrafish Proteins