Unraveling plant hormone signaling through the use of small molecules

Abstract

Plants have acquired the capacity to grow continuously and adjust their morphology in response to endogenous and external signals, leading to a high architectural plasticity. The dynamic and differential distribution of phytohormones is an essential factor in these developmental changes. Phytohormone perception is a fast but complex process modulating specific developmental reprogramming. In recent years, chemical genomics or the use of small molecules to modulate target protein function has emerged as a powerful strategy to study complex biological processes in plants such as hormone signaling. Small molecules can be applied in a conditional, dose-dependent and reversible manner, with the advantage of circumventing the limitations of lethality and functional redundancy inherent to traditional mutant screens. High-throughput screening of diverse chemical libraries has led to the identification of bioactive molecules able to induce plant hormone-related phenotypes. Characterization of the cognate targets and pathways of those molecules has allowed the identification of novel regulatory components, providing new insights into the molecular mechanisms of plant hormone signaling. An extensive structure-activity relationship (SAR) analysis of the natural phytohormones, their designed synthetic analogs and newly identified bioactive molecules has led to the determination of the structural requirements essential for their bioactivity. In this review, we will summarize the so far identified small molecules and their structural variants targeting specific phytohormone signaling pathways. We will highlight how the SAR analyses have enabled better interrogation of the molecular mechanisms of phytohormone responses. Finally, we will discuss how labeled/tagged hormone analogs can be exploited, as compelling tools to better understand hormone signaling and transport mechanisms.

Small‐molecule auxin inhibitors that target YUCCA are powerful tools for studying auxin function

“…Chemical genetics is a powerful alternative strategy that employs small molecules as probes to dissect biological processes (Dejonghe and Russinova, 2014;Rigal et al, 2014). These small chemicals can be applied to any tissue and anytime in the life cycle, with appropriate concentrations of chemicals, to knock down a targeted protein.…”

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

“…Our study thus brings us a step closer to a better quantitative understanding of the TIR1-AUX/IAA interaction system of auxin perception in a tissue-specific manner. Besides IAA, several other phytohormones including jasmonate-isoleucine, gibberellin, brassinosteroids and abscisic acid (ABA), also function by modulating the protein-protein interactions of their co-receptors (67). Isolation of novel molecules modulating the interactions of coreceptor complexes could therefore also be useful in uncovering the signaling components of these phytohormones.…”

Shaping Small Bioactive Molecules to Untangle Their Biological Function: A Focus on Fluorescent Plant Hormones

“…To reach this aim, they introduced a NBD fluorophore moiety into 5-hydroxy-IAA and 7-hydroxy-NAA on the ground that alkoxy substitution on that position did not affect their transport through AUX1, PIN, and ABCBs auxin transporters but rendered the analogues inactive at auxin receptors ( Figure 8) (Tsuda et al, 2011). Indeed, several anti-auxin molecules have been developed by inserting bulky groups on the alpha carbon of IAA: such compounds bind with TIR1 receptors as natural IAA but prevent the interaction with co-receptors Aux/IAA required to induce bioactivity (Rigal et al, 2014). Interestingly, loss of bioactivity which is usually seen as an adverse consequence of fluorophore binding is here a specific requirement of the designed conjugate.…”