title: Farnesol-mediated shift in the metabolic origin of prenyl groups used for protein prenylation in plants.
abstract: Little is known about how plant cells regulate the exchange of prenyl diphosphates between the two compartmentalized isoprenoid biosynthesis pathways. Prenylation of proteins is a suitable model to study such interactions between the plastidial methylerythritol phosphate (MEP) and the cytosolic mevalonate (MVA) pathways because prenyl moieties used to modify proteins rely on both origins. Tobacco cells expressing a prenylatable GFP were treated with specific MEP and/or MVA pathways inhibitors to block the formation of prenyl diphosphates and therefore the possibility to modify the proteins. Chemical complementation assays using prenyl alcohol precursors restore the prenylation. Indeed, geranylgeraniol (C20 prenyl alcohol) and to a lesser but significant level C15-farnesol restored the prenylation of a protein bearing a geranylgeranylation CaaX motif, which under standard conditions is modified by a MEP-derived prenyl group. However, the restoration takes place in different ways. While geranylgeraniol operates directly as a metabolic precursor, the C15-prenyl alcohol functions indirectly as a signal that leads to shift the metabolic origin of prenyl groups in modified proteins, here from the plastidial MEP pathway in favor of the cytosolic MVA pathway. Furthermore, farnesol interferes negatively with the MEP pathway in an engineered Escherichia coli strain synthesizing isoprenoids either starting from MVA or from MEP. Following the cellular uptake of a fluorescent analog of farnesol, we showed its close interaction with tobacco plastids and modification of plastid homeostasis. As a consequence, in tobacco farnesol supposedly inhibits the plastidial MEP pathway and activates the cytosolic MVA pathway, leading to the shift in the metabolic origin and thereby acts as a potential regulator of crosstalk between the two pathways. Together, those results suggest a new role for farnesol (or a metabolite thereof) as a central molecule for the regulation of isoprenoid biosynthesis in plants.
authors.affiliation: CNRS, Institut de biologie moléculaire des plantes conventionné avec l'Unistra, F-67084 Strasbourg, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Huchelmann
authors.affiliation: CNRS, Institut de biologie moléculaire des plantes conventionné avec l'Unistra, F-67084 Strasbourg, France.
authors.forename: Mathieu Semir
authors.initials: MS
authors.lastname: Brahim
authors.affiliation: CNRS, Institut de biologie moléculaire des plantes conventionné avec l'Unistra, F-67084 Strasbourg, France.
authors.forename: Esther
authors.initials: E
authors.lastname: Gerber
authors.affiliation: CNRS/Unistra, Institut Le Bel, 4 rue Blaise Pascal, F-67081 Strasbourg, France.
authors.forename: Denis
authors.initials: D
authors.lastname: Tritsch
authors.affiliation: CNRS, Institut de biologie moléculaire des plantes conventionné avec l'Unistra, F-67084 Strasbourg, France.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Bach
authors.affiliation: CNRS, Institut de biologie moléculaire des plantes conventionné avec l'Unistra, F-67084 Strasbourg, France. Electronic address: andrea.hemmerlin@ibmp-cnrs.unistra.fr.
authors.forename: Andréa
authors.initials: A
authors.lastname: Hemmerlin
mesh_terms: D002460:Cell Line; D004896:Erythritol / Q000031:analogs & derivatives / Q000378:metabolism; D005204:Farnesol / Q000378:metabolism*; D010940:Plant Proteins / Q000737:chemistry / Q000378:metabolism*; D018087:Plastids / Q000378:metabolism; D017368:Protein Prenylation; D013403:Sugar Phosphates / Q000378:metabolism
chemical_list: C114232:2-C-methylerythritol 4-phosphate; D010940:Plant Proteins; D013403:Sugar Phosphates; D005204:Farnesol; D004896:Erythritol
keywords: Farnesol; Isoprenoid biosynthesis; Methylerythritol phosphate; Mevalonate; Plants; Protein prenylation