Selective auxin agonists induce specific AUX/IAA protein degradation to modulate plant development

Abstract

Auxin phytohormones control most aspects of plant development through a complex and interconnected signaling network. In the presence of auxin, AUXIN/INDOLE-3-ACETIC ACID (AUX/IAA) transcriptional repressors are targeted for degradation by the SKP1-CULLIN1-F-BOX (SCF) ubiquitin-protein ligases containing TRANSPORT INHIBITOR RESISTANT 1/AUXIN SIGNALING F-BOX (TIR1/AFB). CULLIN1-neddylation is required for SCFTIR1/AFBfunctionality, as exemplified by mutants deficient in the NEDD8-activating enzyme subunit AUXIN-RESISTANT 1 (AXR1). Here, we report a chemical biology screen that identifies small molecules requiring AXR1 to modulate plant development. We selected four molecules of interest, RubNeddin 1 to 4 (RN1 to -4), among which RN3 and RN4 trigger selective auxin responses at transcriptional, biochemical, and morphological levels. This selective activity is explained by their ability to consistently promote the interaction between TIR1 and a specific subset of AUX/IAA proteins, stimulating the degradation of particular AUX/IAA combinations. Finally, we performed a genetic screen using RN4, the RN with the greatest potential for dissecting auxin perception, which revealed that the chromatin remodeling ATPase BRAHMA is implicated in auxin-mediated apical hook development. These results demonstrate the power of selective auxin agonists to dissect auxin perception for plant developmental functions, as well as offering opportunities to discover new molecular players involved in auxin responses.

New fluorescent auxin probes visualise tissue‐specific and subcellular distributions of auxin in Arabidopsis

“…Here we present fluorescent auxin analogues derived from 2,4‐D and labelled with NBD using two different linkers that are attached via the side‐chain carboxyl group of the 2,4‐D with an amide bond. Our concurrent study presenting structures similar to FluorA compounds, being 2,4‐D and 2,4,5‐T derivatives bearing the same PIP linker and a cysteamine aliphatic linker, showed these structures to be sterically favourable for binding to the TIR1‐AUX/IAA7 co‐receptor system in pull‐down assays (Vain et al ., 2019). An extensive SPR analysis revealed that various auxin agonists, including chlorinated auxin derivatives, can differently stabilise the co‐receptor system depending on the F‐box‐AUX/IAA partners, but that IAA conjugates were inactive (Lee et al ., 2014).…”

Auxin and its role in plant development: structure, signalling, regulation and response mechanisms

“…The TIR and AFB proteins are auxin-sensitive nuclear proteins, which have nucleotide/leucine-rich repeat sites that allow interactions with a specific subset of Aux/IAA proteins (Vain et al, 2019). Studies with Arabidopsis have shown that TIR1/ AFB genes encode major auxin receptors that regulate plant growth, and that AFB3 mediates lateral root growth in response to nitrogen (Vidal et al, 2013).…”

New Wine in an Old Bottle: Utilizing Chemical Genetics to Dissect Apical Hook Development

“…Besides transport, uxin perception is also a key regulating point for apical hook development. Several chemical regulators that target the auxin receptor have been reported, such as auxinole as an antagonist [ 69 ], fluorescent auxin analogs [ 70 ], and selective agonists for specific subsets of AUX/IAA [ 71 ], among which auxinole was applied to dissect the developmental processes of the apical hook [ 15 ]. In addition, an orthogonal auxin–TIR1 receptor pair (convex IAA–concave TIR1) has been developed [ 72 ], providing a strategy for the precise manipulation of auxin signal.…”