title: Immunophilin-like TWISTED DWARF1 modulates auxin efflux activities of Arabidopsis P-glycoproteins.
abstract: The immunophilin-like protein TWISTED DWARF1 (TWD1/FKBP42) has been shown to physically interact with the multidrug resistance/P-glycoprotein (PGP) ATP-binding cassette transporters PGP1 and PGP19 (MDR1). Overlapping phenotypes of pgp1/pgp19 and twd1 mutant plants suggested a positive regulatory role of TWD1 in PGP-mediated export of the plant hormone auxin, which controls plant development. Here, we provide evidence at the cellular and plant levels that TWD1 controls PGP-mediated auxin transport. twd1 and pgp1/pgp19 cells showed greatly reduced export of the native auxin indole-3-acetic acid (IAA). Constitutive overexpression of PGP1 and PGP19, but not TWD1, enhanced auxin export. Coexpression of TWD1 and PGP1 in yeast and mammalian cells verified the specificity of the regulatory effect. Employing an IAA-specific microelectrode demonstrated that IAA influx in the root elongation zone was perturbed and apically shifted in pgp1/pgp19 and twd1 roots. Mature roots of pgp1/pgp19 and twd1 plants revealed elevated levels of free IAA, which seemed to account for agravitropic root behavior. Our data suggest a novel mode of PGP regulation via FK506-binding protein-like immunophilins, implicating possible alternative strategies to overcome multidrug resistance.
authors.affiliation: Zurich-Basel Plant Science Center, University of Zurich, Institute of Plant Biology, and Molecular Plant Physiology, CH-8008 Zurich, Switzerland.
authors.forename: Rodolphe
authors.initials: R
authors.lastname: Bouchard
authors.forename: Aurélien
authors.initials: A
authors.lastname: Bailly
authors.forename: Joshua J
authors.initials: JJ
authors.lastname: Blakeslee
authors.forename: Sophie C
authors.initials: SC
authors.lastname: Oehring
authors.forename: Vincent
authors.initials: V
authors.lastname: Vincenzetti
authors.forename: Ok Ran
authors.initials: OR
authors.lastname: Lee
authors.forename: Ivan
authors.initials: I
authors.lastname: Paponov
authors.forename: Klaus
authors.initials: K
authors.lastname: Palme
authors.forename: Stefano
authors.initials: S
authors.lastname: Mancuso
authors.forename: Angus S
authors.initials: AS
authors.lastname: Murphy
authors.forename: Burkhard
authors.initials: B
authors.lastname: Schulz
authors.forename: Markus
authors.initials: M
authors.lastname: Geisler
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000737:chemistry*; D017360:Arabidopsis / Q000502:physiology*; D029681:Arabidopsis Proteins / Q000502:physiology*; D005656:Fungal Proteins / Q000737:chemistry; D018506:Gene Expression Regulation, Plant; D006367:HeLa Cells; D006801:Humans; D020104:Immunophilins / Q000737:chemistry; D007210:Indoleacetic Acids / Q000737:chemistry; D008954:Models, Biological; D009154:Mutation; D018517:Plant Roots / Q000378:metabolism; D011485:Protein Binding; D022021:Tacrolimus Binding Proteins / Q000737:chemistry / Q000502:physiology*
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D029681:Arabidopsis Proteins; D005656:Fungal Proteins; D007210:Indoleacetic Acids; C471286:TWD1 protein, Arabidopsis; D022021:Tacrolimus Binding Proteins; D020104:Immunophilins