Cytokinin and Ethylene Cell Signaling Pathways from Prokaryotes to Eukaryotes

Abstract

Cytokinins (CKs) and ethylene (ET) are among the most ancient organic chemicals on Earth. A wide range of organisms including plants, algae, fungi, amoebae, and bacteria use these substances as signaling molecules to regulate cellular processes. Because of their ancestral origin and ubiquitous occurrence, CKs and ET are also considered to be ideal molecules for inter-kingdom communication. Their signal transduction pathways were first historically deciphered in plants and are related to the two-component systems, using histidine kinases as primary sensors. Paradoxically, although CKs and ET serve as signaling molecules in different kingdoms, it has been supposed for a long time that the canonical CK and ET signaling pathways are restricted to terrestrial plants. These considerations have now been called into question following the identification over recent years of genes encoding CK and ET receptor homologs in many other lineages within the tree of life. These advances shed new light on the dissemination and evolution of these hormones as both intra- and inter-specific communication molecules in prokaryotic and eukaryotic organisms.

Keywords: cell signaling; cytokinins; ethylene; histidine kinases; receptors.

Figure 1

Perception and transduction of cytokinin (CK) and ethylene (ET) signals in the model plant Arabidopsis. (A) The cytokinin signaling pathway. The perception of CKs in Arabidopsis primarily involves the perception of these hormones by dimerized receptors such as the CRE1 receptor via the cyclase/histidine kinase-associated sensing extracellular (CHASE) domain. CRE1 then auto-phosphorylates (histidine kinase (HK) activity) and immediately transfers its phosphate group to the conserved histidine of a protein belonging to the histidine-containing phosphotransfer (HPt) family. This small protein then acts as a cytoplasm-to-nucleus shuttle and in turn phosphorylates a type B response regulator, which, when activated, positively regulates the transcription of response genes to the CK signal. (B) The ET signaling pathway. Ethylene molecules are detected by ethylene receptors (epitomized here by ETR1) with ethylene binding to the three transmembrane helices (in sky blue). Binding of ET to the dimerized ETR1 receptor downregulates its activity. In the absence of ET, ETR1 activates the serine/threonine kinase CTR1. The CTR1 protein then phosphorylates the EIN2 protein located in the ER membrane, leading to the proteolysis of EIN2. In the presence of ET, ETR1 activity is reduced, leading to less CTR1 activity; this leads to lower phosphorylation and accumulation of EIN2 protein and subsequent activation of the EIN3 and related transcription factors. EIN3 then positively regulates the transcription of ET signal response genes. (C) The domain structure of the Arabidopsis ET (ETR1) and CK (CRE1) receptors.

Figure 2

Current knowledge concerning CKs and ET signaling in bacteria. (A) In the phytopathogenic bacterium Xanthomonas campestris, PcrK is a CHASE-domain-containing HK receptor that binds the plant-produced CK N⁶-isopentenyladenine (iP). iP perception decreases PcrK HK activity and concomitantly the phosphorylation level of PcrR, the cognate RR of PcrK, to promote the phosphodiesterase activity of PcrR in degrading the second messenger (3′,5′-cyclic di-guanylic acid). This four-step phosphorelay signaling chain improves bacterial tolerance to oxidative stress by orchestrating the expression of a series of virulence-associated genes. (B) In the cyanobacterium Nostoc sp., all2875 is a CHASE-domain-containing HK receptor that moderately binds iP and, with lower affinity, trans-zeatin. (C) ET signaling in the cyanobacterium Synechocystis sp. ET negatively regulates the ETR-like protein slr1212, which putatively signals to a downstream response regulator protein, slr1213. The GAF domain binds a chromophore and functions as a light receptor, making this a bifunctional receptor. (D) Some other examples of domain arrangement for CK and ET receptor homologs found in various bacteria.

Figure 3

CK and ET signaling pathways potentially present in Opisthokonta. (A) The Mesomycetozoa Capsaspora owczarzaki is a representative of the closest known unicellular clade to animals. A recent phylogenomic analysis identified an ET receptor homolog in this species, CowczHK2. (B) A putative CK receptor was recently identified in the clade of Glomeromycotina. (C) Glomeromycota genomes also encode homologs of plant ET receptors, but their functions remain undefined. For a domain key, please refer to Figure 2.

Figure 4

CKs produced in slime molds and CK and ET signaling modules in Amoebozoa. (A) Six different CKs were identified recently in the slime mold D. discoideum. CKs were previously shown to coordinately orchestrate the different developmental stages of this social amoeba, especially spore formation. (B) The D. discoideum DhkA histidine kinase sensor contains a CHASE domain and was also shown to play a role in the CK-controlled sporulation process. To date, genetic evidence for a role for DhkA in transmitting the CK signal is still lacking. (C) Recent phylogenomic analysis revealed the presence of ET receptor homologs in free-living amoebae (Acanthamoeba and Balamuthia sp.), but not in other Amoebozoa clades.

Figure 5

Examples of domain arrangements for CK and ET receptor homologs found in various members of the Stramenopiles, Alveolates, and Rhizaria (SAR) supergroup.