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Prieurianin/endosidin 1 is an actin‐stabilizing small molecule identified from a chemical genetic screen for circadian clock effectors in Arabidopsis thaliana
Author(s) -
Tóth Réka,
GerdingReimers Claas,
Deeks Michael J.,
Menninger Sascha,
Gallegos Rafael M.,
Tonaco Isabella A. N.,
Hübel Katja,
Hussey Patrick J.,
Waldmann Herbert,
Coupland George
Publication year - 2012
Publication title -
the plant journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.058
H-Index - 269
eISSN - 1365-313X
pISSN - 0960-7412
DOI - 10.1111/j.1365-313x.2012.04991.x
Subject(s) - microbiology and biotechnology , actin , effector , arabidopsis thaliana , biology , actin cytoskeleton , arabidopsis , circadian clock , actin remodeling , cytoskeleton , microfilament , chemistry , circadian rhythm , biochemistry , cell , neuroscience , gene , mutant
Summary 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.