title: Prieurianin/endosidin 1 is an actin-stabilizing small molecule identified from a chemical genetic screen for circadian clock effectors in Arabidopsis thaliana.
abstract: Chemical modulators are powerful tools to investigate biological processes. To identify circadian clock effectors, we screened a natural product library in the model plant Arabidopsis thaliana. Two compounds, prieurianin (Pri) and prieurianin acetate, were identified as causing a shorter circadian period. Recently, Pri was independently identified as a vesicle trafficking inhibitor and re-named endosidin 1 (ES1). Here we show that Pri primarily affects actin filament flexibility in vivo, later resulting in reduced severing and filament depolymerization. This stabilization of the actin cytoskeleton subsequently causes changes in vesicle trafficking. Pri also affected microfilaments in mammalian cells, indicating that its target is highly conserved; however, it did not alter actin dynamics in vitro, suggesting that its activity requires the presence of actin-associated proteins. Furthermore, well-characterized actin inhibitors shortened the period length of the Arabidopsis clock in a similar way to Pri, supporting the idea that Pri affects rhythms by altering the actin network. We conclude that actin-associated processes influence the circadian system in a light-dependent manner, but their disruption does not abolish rhythmicity. In summary, we propose that the primary effect of Pri is to stabilize the actin cytoskeleton system, thereby affecting endosome trafficking. Pri appears to stabilize actin filaments by a different mechanism from previously described inhibitors, and will be a useful tool to study actin-related cellular processes.
authors.affiliation: Department of Plant Developmental Biology, Max Planck Institute for Plant Breeding Research, Cologne, Germany. toth@mpipz.mpg.de
authors.forename: Réka
authors.initials: R
authors.lastname: Tóth
authors.forename: Claas
authors.initials: C
authors.lastname: Gerding-Reimers
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Deeks
authors.forename: Sascha
authors.initials: S
authors.lastname: Menninger
authors.forename: Rafael M
authors.initials: RM
authors.lastname: Gallegos
authors.forename: Isabella A N
authors.initials: IA
authors.lastname: Tonaco
authors.forename: Katja
authors.initials: K
authors.lastname: Hübel
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Hussey
authors.forename: Herbert
authors.initials: H
authors.lastname: Waldmann
authors.forename: George
authors.initials: G
authors.lastname: Coupland
mesh_terms: D008841:Actin Cytoskeleton / Q000187:drug effects* / Q000378:metabolism; D000199:Actins / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D017360:Arabidopsis / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects / Q000648:ultrastructure; D002460:Cell Line; D002522:Chlorocebus aethiops; D057906:Circadian Clocks / Q000187:drug effects*; D005820:Genetic Testing; D018546:Hypocotyl / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects / Q000648:ultrastructure; D008027:Light; D036701:Limonins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D018613:Microscopy, Confocal; D008855:Microscopy, Electron, Scanning; D030821:Plants, Genetically Modified; D036226:Seedlings / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects / Q000648:ultrastructure; D054852:Small Molecule Libraries; D013997:Time Factors; D022161:Transport Vesicles / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000199:Actins; D036701:Limonins; D054852:Small Molecule Libraries; C105838:prieurianin