Heterotrimeric G protein-coupled signaling in plants

Abstract

Investigators studying G protein-coupled signaling--often called the best-understood pathway in the world owing to intense research in medical fields--have adopted plants as a new model to explore the plasticity and evolution of G signaling. Much research on plant G signaling has not disappointed. Although plant cells have most of the core elements found in animal G signaling, differences in network architecture and intrinsic properties of plant G protein elements make G signaling in plant cells distinct from the animal paradigm. In contrast to animal G proteins, plant G proteins are self-activating, and therefore regulation of G activation in plants occurs at the deactivation step. The self-activating property also means that plant G proteins do not need and therefore do not have typical animal G protein-coupled receptors. Targets of activated plant G proteins, also known as effectors, are unlike effectors in animal cells. The simpler repertoire of G signal elements in Arabidopsis makes G signaling easier to manipulate in a multicellular context.

Figure 1

Intrinsic properties and regulatory systems of animal and plant G proteins. (a) The animal model. An animal G protein forms an inactive heterotrimer in the steady state. Ligand-bound G protein–coupled receptors (GPCRs) promote nucleotide exchange on the Gα subunit, and GTP-bound Gα separates from the Gβγ dimer. Both the GTP-bound Gα and the freed Gβγ regulate the activity of the effectors. Gα hydrolyzes GTP, returns to the GDP-bound state, and then re-forms the inactive heterotrimer with Gβγ. Regulator of G protein signaling (RGS) proteins accelerate GTP hydrolysis by Gα. The numbers (min⁻¹) beside the black arrows show the intrinsic rates of GDP/GTP exchange and GTP hydrolysis. (b) The Arabidopsis model. The Arabidopsis Gα protein, AtGPA1, spontaneously exchanges its GDP for GTP without GPCRs but does not readily hydrolyze GTP without GTPase-accelerating proteins (GAPs). A seven-transmembrane (7TM) RGS protein, AtRGS1, constitutively promotes the intrinsically slow hydrolysis reaction by AtGPA1. (c) A structural basis for the self-activating property of AtGPA1 (Protein Data Bank 2XTZ). The Ras domain (red) has similarity to small GTPases. It contains sites for binding to guanine nucleotides, effectors, and RGS proteins. The helical domain (yellow) shields the guanine nucleotide (blue) bound on the Ras domain. Ligand-bound GPCRs in animals or spontaneous fluctuations in Arabidopsis change the orientation of the helical domain, leaving the guanine nucleotide exposed, which leads to dissociation from the Ras domain. Blue arrows indicate spontaneous fluctuation of the helical domain, which confers the self-activating property of AtGPA1. Models in panels a and b adapted from Reference .

Figure 2

Models of potential regulators of G proteins. The thin curved arrows represent rate-limiting reactions, and the thick curved arrows represent non-rate-limiting reactions. The regulatory molecules that operate on these reactions are shown above and below the curved arrows. The active G protein is shown as a “G” with a bound GTP. The inactive G protein is bound by GDP. (a) In animals, activation of G proteins is regulated by a guanine nucleotide exchange factor (GEF) that speeds up the release of bound GDP. (b) In plants other than cereals, a seven-transmembrane (7TM) regulator of G protein signaling (RGS) protein speeds up the rate-limiting reaction of hydrolysis. Plants may also utilize a GDP dissociation inhibitor (GDI), which slows nucleotide exchange. (c) Cereals lack canonical RGS proteins; therefore, if the rate-limiting GTP hydrolysis is regulated, it is by an unknown mechanism and protein. (d) In liverworts, both nucleotide exchange and hydrolysis are fast. The mechanism for regulating the active state of G proteins is unknown and without precedent.

Figure 3

Two models for integrating comprehensive G signals. (a) A bottleneck issue in plant G signaling. Plant G proteins process multiple signaling inputs, despite the small repertoire of the G signaling complex. How plant cells sort these inputs out to the appropriate signaling pathways remains unknown. Abbreviations: PAMP, pathogen-associated molecular pattern; ROS, reactive oxygen species. (b,c) Two models that fit the observations. The molecular rheostat model (panel b) modulates different physiological functions. G proteins sense the nutrient status—in this case, the sugar concentration, depicted as the input at the bottom of the rheostat. The nutrient status determines the activation level of the G proteins (the operating arm of the rheostat), then alters the cellular responses in multiple physiological events (the contacts of the rheostat). This model allows G proteins to affect many physiological events without a direct coupling to specific receptors. Only one signaling pathway is shown, but the concept is applicable to others as well. In the mix-and-match model (panel c), phosphorylation and endocytosis of Arabidopsis regulator of G protein signaling 1 (AtRGS1) cause sustained activation of G signaling by physically uncoupling the seven-transmembrane (7TM) receptor GTPase-accelerating protein (GAP) from the self-activating G protein. In this model, different receptor kinases may indirectly activate G signaling by phosphorylating the 7TM receptor GAP and causing endocytosis of AtRGS1. In this model, each receptor may form a signaling complex with a specific effector of G signaling. This allows a small number of G protein complexes to control various pathways and cellular responses through a single G protein complex.