title: ATP-binding cassette transporter controls leaf surface secretion of anticancer drug components in Catharanthus roseus.
abstract: The Madagascar periwinkle (Catharanthus roseus) is highly specialized for the biosynthesis of many different monoterpenoid indole alkaloids (MIAs), many of which have powerful biological activities. Such MIAs include the commercially important chemotherapy drugs vinblastine, vincristine, and other synthetic derivatives that are derived from the coupling of catharanthine and vindoline. However, previous studies have shown that biosynthesis of these MIAs involves extensive movement of metabolites between specialized internal leaf cells and the leaf epidermis that require the involvement of unknown secretory processes for mobilizing catharanthine to the leaf surface and vindoline to internal leaf cells. Spatial separation of vindoline and catharanthine provides a clear explanation for the low levels of dimers that accumulate in intact plants. The present work describes the molecular cloning and functional identification of a unique catharanthine transporter (CrTPT2) that is expressed predominantly in the epidermis of young leaves. CrTPT2 gene expression is activated by treatment with catharanthine, and its in planta silencing redistributes catharanthine to increase the levels of catharanthine-vindoline drug dimers in the leaves. Phylogenetic analysis shows that CrTPT2 is closely related to a key transporter involved in cuticle assembly in plants and that may be unique to MIA-producing plant species, where it mediates secretion of alkaloids to the plant surface.
authors.affiliation: Department of Biological Sciences, Brock University, St. Catharines, ON, Canada L2S 3A1.
authors.forename: Fang
authors.initials: F
authors.lastname: Yu
authors.forename: Vincenzo
authors.initials: V
authors.lastname: De Luca
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000970:Antineoplastic Agents / Q000378:metabolism*; D001692:Biological Transport; D030008:Catharanthus / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D018506:Gene Expression Regulation, Plant; D020868:Gene Silencing; D017343:Genes, Plant / Q000235:genetics; D008969:Molecular Sequence Data; D010802:Phylogeny; D019441:Plant Epidermis / Q000235:genetics / Q000378:metabolism*; D018515:Plant Leaves / Q000378:metabolism*; D010940:Plant Proteins / Q000235:genetics / Q000378:metabolism*; D010942:Plant Viruses / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D014748:Vinca Alkaloids / Q000378:metabolism
chemical_list: D018528:ATP-Binding Cassette Transporters; D000970:Antineoplastic Agents; D010940:Plant Proteins; D014748:Vinca Alkaloids; D000255:Adenosine Triphosphate; C017836:catharanthine
keywords: gene duplication; metabolic diversification; plasma membrane ABC-PDR-alkaloid transporter; secretion to plant surfaces
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