Gibberellin-GID1-DELLA: A Pivotal Regulatory Module for Plant Growth and Development

Abstract

The diterpenoid hormone GA controls diverse developmental processes throughout the life cycle of a plant. Physiological and genetic studies show that active GA promotes seed germination and vegetative growth. In some species, GA also induces flowering and regulates flower, fruit, and seed development. This article highlights recent advances in our understanding of the molecular mechanisms of GA metabolism, transport, perception, and signaling, and the regulatory circuit between the GA pathway and other pathways to control plant growth and development in response to internal and external cues. The biochemical pathway of GA biosynthesis and catabolism in plants is well defined, and genes encoding most enzymes in this pathway have been identified (Yamaguchi, 2008). Although many GA derivatives are present in a given plant, only very few GAs are biologically active. GA biosynthesis appears to be tightly linked to the site of GA responses as bioactive GAs have been found to be more abundant in rapidly growing tissues (Yamaguchi, 2008). This idea is also supported by recent studies on the expression of GA metabolism genes and phenotypic characterization of GA-deficient mutants (Sun, 2008; Yamaguchi, 2008). However, transport of GA intermediates or active GAs may also play an important role in modulating GA responses. For example, the cereal aleurone is well known for its response to embryo-produced GA (namely expression of hydrolytic enzyme genes in this tissue). In Arabidopsis (Arabidopsis thaliana), GA4 (the major bioactive GA in this plant) can be transported from rosette leaves to the shoot apex to facilitate flower initiation in Arabidopsis (Eriksson et al., 2006). This was demonstrated by feeding labeled GA4 to leaves and then measuring GA4 levels in the shoot apical meristem. GA 3-oxidase (GA3ox) catalyzes the final step for bioactive GA production. Studies of GA3ox mutants suggest that bioactive GAs made in the stamens and/or flower receptacles are transported to petals to promote their growth in Arabidopsis (Hu et al., 2008). In developing siliques, active GAs are transported from the seed endosperm to the surrounding maternal tissues where they promote fruit growth. In germinating seeds, a subset of the GA-responsive genes are expressed in different cell types from those of GA3ox genes, also suggesting that GAs need to be transported between cells to regulate gene expression (Ogawa et al., 2003). It will be important to investigate the molecular mechanism of GA transport and how GA metabolism and transport are coordinated to modulate the local GA levels in response to the internal developmental program and environmental cues. Development of gene markers and/or fluorescent sensors to monitor bioactive GA molecules in planta will greatly facilitate these studies. Recent genetic, biochemical, and structural studies have elucidated the molecular mechanism of GA perception and initial steps in GA signaling in plants (Fig. 1; Ueguchi-Tanaka et al., 2007; Sun, 2008). The GA signal is perceived by the GA receptor GID1 (for GA INSENSITIVE DWARF1), which is a soluble protein that is localized to both cytoplasm and nucleus. DELLA proteins are nuclear transcriptional regulators, which repress GA signaling and restrict plant growth presumably by causing transcriptional reprogramming. Binding of GA to GID1 enhances the interaction between GID1 and DELLA, resulting in rapid degradation of DELLAs via the ubiquitin-proteasome pathway. A specific ubiquitin E3 ligase complex (SCFSLY1/GID2) is required to recruit DELLA for polyubiquitination and subsequent degradation by the 26S proteasome. Recently, crystal structures of GA-GID1 and GA-GID1-DELLA complexes have been determined (Murase et al., 2008; Shimada et al., 2008). Without GA binding, the N-terminal extension (N-Ex) of GID1 has a flexible structure that is highly sensitive to protease treatment. Binding of GA to the C-terminal domain of GID1 induces a conformational switch of its N-Ex to cover the GA-binding pocket (like closing the lid), as well as creates hydrophobic surfaces for DELLA binding (Fig. 1). Although there is no direct contact between DELLA and GA, DELLA binding further stabilizes the GA-GID1-DELLA complex. These studies indicate that bioactive GA is an allosteric inducer of its receptor GID1. The current model also suggests that binding of GA-GID1 to DELLA enhances recognition of DELLA by the F-box protein of the ubiquitin E3 ligase SCF complex (SLY1 in Arabidopsis and GID2 in rice [Oryza sativa]; Fig. 1). This is different from the mechanism of auxin perception: Auxin functions as a molecular glue that brings the F-box protein (TIR1 and its homologs) and its substrate protein (IAA/AUX) together without altering the conformations of these proteins (Tan et al., 2007). Model of GA signaling in plants. Bioactive GA binding induces a conformational switch in the N-Ex of GID1 for DELLA binding, which in turn promotes a conformational transition in the GRAS