title: Sortin1-hypersensitive mutants link vacuolar-trafficking defects and flavonoid metabolism in Arabidopsis vegetative tissues.
abstract: Sortin1 is a chemical genetic-hit molecule that causes specific mislocalization of plant and yeast-soluble and membrane vacuolar markers. To better understand its mode of action, we designed a Sortin1-hypersensitive screen and identified several Sortin1-hypersensitive and flavonoid-defective mutants. Mechanistically, Sortin1 mimics the effect of the glutathione inhibitor buthionine sulfoximine and alters the vacuolar accumulation of flavonoids, likely blocking their transport through vacuole-localized ABC transporters. Structure-activity relationship studies conducted in Arabidopsis revealed the structural requirements for Sortin1 bioactivity and demonstrated that overlapping Sortin1 substructures can be used to discriminate between vacuolar-flavonoid accumulations and vacuolar-biogenesis defects. We conclude that Sortin1 is a valuable probe for dissecting novel links among flavonoid transport, vacuolar integrity, and the trafficking of vacuolar targeted cargoes in Arabidopsis.
authors.affiliation: Center for Plant Cell Biology and Department of Botany and Plant Sciences, University of California-Riverside, CA 92521, USA.
authors.forename: Abel
authors.initials: A
authors.lastname: Rosado
authors.forename: Glenn R
authors.initials: GR
authors.lastname: Hicks
authors.forename: Lorena
authors.initials: L
authors.lastname: Norambuena
authors.forename: Ilana
authors.initials: I
authors.lastname: Rogachev
authors.forename: Sagit
authors.initials: S
authors.lastname: Meir
authors.forename: Lucille
authors.initials: L
authors.lastname: Pourcel
authors.forename: Jan
authors.initials: J
authors.lastname: Zouhar
authors.forename: Michelle Q
authors.initials: MQ
authors.lastname: Brown
authors.forename: Marietta P
authors.initials: MP
authors.lastname: Boirsdore
authors.forename: Rachel S
authors.initials: RS
authors.lastname: Puckrin
authors.forename: Sean R
authors.initials: SR
authors.lastname: Cutler
authors.forename: Enrique
authors.initials: E
authors.lastname: Rojo
authors.forename: Asaph
authors.initials: A
authors.lastname: Aharoni
authors.forename: Natasha V
authors.initials: NV
authors.lastname: Raikhel
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D017360:Arabidopsis / Q000166:cytology* / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D001692:Biological Transport / Q000187:drug effects; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D005419:Flavonoids / Q000096:biosynthesis / Q000378:metabolism*; D005978:Glutathione / Q000096:biosynthesis / Q000378:metabolism; D007192:Indenes / Q000737:chemistry / Q000494:pharmacology*; D009154:Mutation; D018384:Oxidative Stress / Q000187:drug effects; D010858:Pigmentation / Q000187:drug effects; D011725:Pyridines / Q000737:chemistry / Q000494:pharmacology*; D011728:Pyridones / Q000737:chemistry; D013329:Structure-Activity Relationship; D014617:Vacuoles / Q000187:drug effects* / Q000378:metabolism*
chemical_list: D018528:ATP-Binding Cassette Transporters; D005419:Flavonoids; D007192:Indenes; D011725:Pyridines; D011728:Pyridones; C558636:sortin1 compound; D019328:Buthionine Sulfoximine; D005978:Glutathione