title: CATP-6, a C. elegans ortholog of ATP13A2 PARK9, positively regulates GEM-1, an SLC16A transporter.
abstract: In previous work, we found that gain-of-function mutations that hyperactivate GEM-1 (an SLC16A transporter protein) can bypass the requirement for GON-2 (a TRPM channel protein) during the initiation of gonadogenesis in C. elegans. Consequently, we proposed that GEM-1 might function as part of a Mg(2+) uptake pathway that functions in parallel to GON-2. In this study, we report that CATP-6, a C. elegans ortholog of the P5B ATPase, ATP13A2 (PARK9), is necessary for gem-1 gain-of-function mutations to suppress the effects of gon-2 inactivation. One possible explanation for this observation is that GEM-1 serves to activate CATP-6, which then functions as a Mg(2+) transporter. However, we found that overexpression of GEM-1 can alleviate the requirement for CATP-6 activity, suggesting that CATP-6 probably acts as a non-essential upstream positive regulator of GEM-1. Our results are consistent with the notion that P5B ATPases govern intracellular levels of Mg(2+) and/or Mn(2+) by regulating the trafficking of transporters and other proteins associated with the plasma membrane.
authors.affiliation: Department of Cell and Developmental Biology, Ludwig-Maximillians-University, Munich, Planegg-Martinsried, Germany.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Lambie
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Tieu
authors.forename: Nadja
authors.initials: N
authors.lastname: Lebedeva
authors.forename: Diane L
authors.initials: DL
authors.lastname: Church
authors.forename: Barbara
authors.initials: B
authors.lastname: Conradt
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000737:chemistry* / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D005838:Genotype; D006066:Gonads / Q000254:growth & development; D008274:Magnesium / Q000378:metabolism; D008969:Molecular Sequence Data; D027501:Monocarboxylic Acid Transporters / Q000235:genetics* / Q000378:metabolism*; D006180:Proton-Translocating ATPases / Q000737:chemistry*; D017385:Sequence Homology; D013489:Suppression, Genetic
chemical_list: C514983:ATP13A2 protein, human; D029742:Caenorhabditis elegans Proteins; C540593:Gem-1 protein, C elegans; D027501:Monocarboxylic Acid Transporters; D000251:Adenosine Triphosphatases; C000588771:CATP-6 protein, C elegans; D006180:Proton-Translocating ATPases; D008274:Magnesium