title: The Candida albicans plasma membrane protein Rch1p, a member of the vertebrate SLC10 carrier family, is a novel regulator of cytosolic Ca2+ homoeostasis.
abstract: Candida albicans RCH1 (regulator of Ca(2+) homoeostasis 1) encodes a protein of ten TM (transmembrane) domains, homologous with human SLC10A7 (solute carrier family 10 member 7), and Rch1p localizes in the plasma membrane. Deletion of RCH1 confers hypersensitivity to high concentrations of extracellular Ca(2+) and tolerance to azoles and Li(+), which phenocopies the deletion of CaPMC1 (C. albicans PMC1) encoding the vacuolar Ca(2+) pump. Additive to CaPMC1 mutation, lack of RCH1 alone shows an increase in Ca(2+) sensitivity, Ca(2+) uptake and cytosolic Ca(2+) level. The Ca(2+) hypersensitivity is abolished by cyclosporin A and magnesium. In addition, deletion of RCH1 elevates the expression of CaUTR2 (C. albicans UTR2), a downstream target of the Ca(2+)/calcineurin signalling. Mutational and functional analysis indicates that the Rch1p TM8 domain, but not the TM9 and TM10 domains, are required for its protein stability, cellular functions and subcellular localization. Therefore Rch1p is a novel regulator of cytosolic Ca(2+) homoeostasis, which expands the functional spectrum of the vertebrate SLC10 family.
authors.affiliation: Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, and National Engineering Laboratory for Cereal Fermentation Technology, School of Biotechnology, Jiangnan University, Wuxi 214122, China. linghuojiang@jiangnan.edu.cn
authors.forename: Linghuo
authors.initials: L
authors.lastname: Jiang
authors.forename: Joerg
authors.initials: J
authors.lastname: Alber
authors.forename: Jihong
authors.initials: J
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Du
authors.forename: Xuexue
authors.initials: X
authors.lastname: Yang
authors.forename: Xichuan
authors.initials: X
authors.lastname: Li
authors.forename: Dominique
authors.initials: D
authors.lastname: Sanglard
authors.forename: Joachim
authors.initials: J
authors.lastname: Geyer
mesh_terms: D002118:Calcium / Q000378:metabolism* / Q000502:physiology; D002176:Candida albicans / Q000235:genetics / Q000502:physiology*; D002462:Cell Membrane / Q000235:genetics / Q000502:physiology*; D003600:Cytosol / Q000378:metabolism / Q000502:physiology; D005656:Fungal Proteins / Q000235:genetics / Q000502:physiology*; D006706:Homeostasis / Q000235:genetics / Q000502:physiology*; D006801:Humans; D005810:Multigene Family; D009154:Mutation; D029363:Organic Anion Transporters, Sodium-Dependent / Q000502:physiology*; D027981:Symporters / Q000502:physiology*
chemical_list: D005656:Fungal Proteins; D029363:Organic Anion Transporters, Sodium-Dependent; C543117:Slc10a7 protein, human; D027981:Symporters; D002118:Calcium