Ethylene signaling pathway is a

signal transduction Signal transduction is the process by which a chemical or physical signal is transmitted through a cell as a biochemical cascade, series of molecular events. Proteins responsible for detecting stimuli are generally termed receptor (biology), rece ...

in plant cells to regulate important growth and developmental processes. Acting as a

plant hormone Plant hormones (or phytohormones) are signal molecules, produced within plants, that occur in extremely low concentrations. Plant hormones control all aspects of plant growth and development, including embryogenesis, the regulation of Organ (anat ...

, the gas

ethylene Ethylene (IUPAC name: ethene) is a hydrocarbon which has the formula or . It is a colourless, flammable gas with a faint "sweet and musky" odour when pure. It is the simplest alkene (a hydrocarbon with carbon–carbon bond, carbon–carbon doub ...

is responsible for promoting the

germination Germination is the process by which an organism grows from a seed or spore. The term is applied to the sprouting of a seedling from a seed of an angiosperm or gymnosperm, the growth of a sporeling from a spore, such as the spores of fungi, ...

of seeds, ripening of fruits, the opening of flowers, the

abscission Abscission () is the shedding of various parts of an organism, such as a plant dropping a leaf, fruit, flower, or seed. In zoology, abscission is the intentional shedding of a body part, such as the shedding of a claw, husk, or the autotomy of a ...

(or shedding) of leaves and stress responses. It is the simplest

alkene In organic chemistry, an alkene, or olefin, is a hydrocarbon containing a carbon–carbon double bond. The double bond may be internal or at the terminal position. Terminal alkenes are also known as Alpha-olefin, α-olefins. The Internationa ...

gas and the first gaseous molecule discovered to function as a hormone. Most of the understanding on ethylene signal transduction come from studies on ''

Arabidopsis thaliana ''Arabidopsis thaliana'', the thale cress, mouse-ear cress or arabidopsis, is a small plant from the mustard family (Brassicaceae), native to Eurasia and Africa. Commonly found along the shoulders of roads and in disturbed land, it is generally ...

''. Ethylene can bind to at least five different membrane gasoreceptors. Although structurally diverse, the ethylene gasoreceptors all exhibit similarity ( homology) to

two-component regulatory system In molecular biology, a two-component regulatory system serves as a basic stimulus-response coupling mechanism to allow organisms to sense and respond to changes in many different environmental conditions. Two-component systems typically co ...

in bacteria, indicating their

common ancestry Common descent is a concept in evolutionary biology applicable when one species is the ancestor of two or more species later in time. According to modern evolutionary biology, all living beings could be descendants of a unique ancestor commonl ...

from bacterial ancestor. Ethylene binds to the gasoreceptors on the cell membrane of the

endoplasmic reticulum The endoplasmic reticulum (ER) is a part of a transportation system of the eukaryote, eukaryotic cell, and has many other important functions such as protein folding. The word endoplasmic means "within the cytoplasm", and reticulum is Latin for ...

. Although

homodimers In biochemistry, a protein dimer is a macromolecular complex or multimer formed by two protein monomers, or single proteins, which are usually non-covalently bound. Many macromolecules, such as proteins or nucleic acids, form dimers. The word ' ...

of the gasoreceptors are required for functional state, only one ethylene molecule binds to each dimer. Unlike in other signal transductions, ethylene is the suppressor of its gasoreceptor activity. Ethylene gasoreceptors are active without ethylene due to binding with other enzymatically active co-gasoreceptors such as constitutive triple response 1 (CTR1) and ethylene insensitive 2 (EIN2). Ethylene binding causes EIN2 to split in two, of which the C-terminal portion of the protein can activate different

transcription factors In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The fun ...

to bring about the effects of ethylene. There is also non-canonical pathway in which ethylene activates cytokinin gasoreceptor, and thereby regulate seed development (

stoma In botany, a stoma (: stomata, from Greek language, Greek ''στόμα'', "mouth"), also called a stomate (: stomates), is a pore found in the Epidermis (botany), epidermis of leaves, stems, and other organs, that controls the rate of gas exc ...

tal aperture) and growth of root (the

apical meristem In cell biology, the meristem is a structure composed of specialized tissue found in plants, consisting of stem cells, known as meristematic cells, which are undifferentiated cells capable of continuous cellular division. These meristematic ce ...

Ethylene gasoreceptors

Ethylene binds to it specific transmembrane gasoreceptor present on the cell membrane of endoplasmic reticulum. There are different ethylene gasoreceptor

isoforms A protein isoform, or "protein variant", is a member of a set of highly similar proteins that originate from a single gene and are the result of genetic differences. While many perform the same or similar biological roles, some isoforms have uniqu ...

. Five isoforms are known in ''Arabidopsis thaliana'' which are named ethylene response/gasoreceptor 1 (ETR1), ethylene response sensor 1 (ERS1), ETR2, ERS2, and ethylene insensitive 4 (EIN4). The ETR1 is similar (

conserved sequence In evolutionary biology, conserved sequences are identical or similar sequences in nucleic acids ( DNA and RNA) or proteins across species ( orthologous sequences), or within a genome ( paralogous sequences), or between donor and receptor taxa ...

) in different plants but with slight amino acid differences. ''A. thaliana'' gasoreceptors are classified into two subfamilies based on genetic relationship and common structural features, namely subfamily 1 that includes ETR1 and ERS1, and subfamily 2 that consists of ETR2, ERS2, and EIN4. In tomato there are seven types of ethylene gasoreceptors named SlETR1, SlETR2, SlETR3, SlETR4, SlETR5, SlETR6, and SlETR7 (Sl for ''

Solanum lycopersicum The tomato (, ), ''Solanum lycopersicum'', is a plant whose fruit is an edible berry that is eaten as a vegetable. The tomato is a member of the nightshade family that includes tobacco, potato, and chili peppers. It originated from and was d ...

,'' the scientific of tomato). All ethylene gasoreceptors have similar organisation: a short N-terminal domain, three conserved transmembrane domains towards the N-terminus, followed by a GAF domain of unknown function, and then signal output motifs in the C-terminal region. The N-terminus is exposed on the lumen of the endoplasmic reticulum, and the C-terminus that is exposed to the cytoplasm of the cell. The N-terminus contains the sites for binding of ethylene, dimerization and membrane localization. Two similar gasoreceptors combine to form a homodimer through a

disulfide bridge In chemistry, a disulfide (or disulphide in British English) is a compound containing a functional group or the anion. The linkage is also called an SS-bond or sometimes a disulfide bridge and usually derived from two thiol groups. In inorg ...

forming a cysteine-cysteine interaction. However, the main membrane localization is done by the transmembrane domain, which can also bind ethylene with the help of copper as a cofactor. Copper ion is supplied by a transmembrane protein responsive-to-antagonist 1 (RAN1) from antioxidant protein 1 (ATX1) via tiplin, or directly by copper transport protein. Although the gasoreceptors are functionally active as dimers, only one copper ion binds to such dimer, indicating that one gasoreceptor dimer binds only one ethylene molecule. Mutations in the binding sites stop ethylene binding and also make plants insensitive to ethylene. Cys-65 in the protein helix 2 is particularly important as the binding site of copper ion as mutation in it stops copper and ethylene binding. The C-terminus is basically a bacterial two-component system with kinase activity and response regulator. ETR1 has

histidine kinase Histidine kinases (HK) are multifunctional, and in non-animal kingdoms, typically transmembrane, proteins of the transferase class of enzymes that play a role in signal transduction across the cellular membrane. The vast majority of HKs are ho ...

activity, whereas ETR2, ERS2, and EIN4 have

serine/threonine kinase A serine/threonine protein kinase () is a kinase enzyme, in particular a protein kinase, that phosphorylates the OH group of the amino-acid residues serine or threonine, which have similar side chains. At least 350 of the 500+ human prote ...

activity, and ERS1 has both. The histidine kinase in ETR1 is not required for ethylene signaling.

Origin and evolution

Ethylene gasoreceptors are functionally similar to bacterial two-component system which has two activation sites named

response regulator In molecular biology, a response regulator is a protein that mediates a cell's response to changes in its environment as part of a two-component regulatory system. Response regulators are coupled to specific histidine kinases which serve as sens ...

and histidine kinase. The cytoplasmic carboxy-terminal part of ethylene gasoreceptor is similar in amino acid sequence to these response regulator and histidine kinase in bacteria; although the N-terminal region is altogether different. Such genetic and protein relationships indicate that gasoreceptors and bacterial two-component gasoreceptors as well as

phytochrome Phytochromes are a class of photoreceptor proteins found in plants, bacteria and fungi. They respond to light in the red and far-red regions of the visible spectrum and can be classed as either Type I, which are activated by far-red light, or ...

s and cytokinin gasoreceptors in plants evolved from and were acquired by plants from a

cyanobacterium Cyanobacteria ( ) are a group of autotrophic gram-negative bacteria that can obtain biological energy via oxygenic photosynthesis. The name "cyanobacteria" () refers to their bluish green (cyan) color, which forms the basis of cyanobacteria' ...

that gave rise to

plastids A plastid is a membrane-bound organelle found in the cells of plants, algae, and some other eukaryotic organisms. Plastids are considered to be intracellular endosymbiotic cyanobacteria. Examples of plastids include chloroplasts (used for photo ...

, the power organelles in plants and protists. Phylogenetic analysis also shows the common origin of the ethylene gasoreceptor in plants and ethylene-binding domain in cyanobacteria. In 2016, Randy F. Lacey and Brad M. Binder at the University of Tennessee discovered that a cyanobacterium, ''Synechocystis'' sp. PCC 6803 response to ethylene signal and has a functional ethylene gasoreceptor, which they named ''Synechocystis'' Ethylene Response1 (SynEtr1). They further showed that SynEtr1 acts similar to plant ethylene gasoreceptor in binding ethylene, indicating the origin of ethylene gasoreceptor from ''Synechocystis''-related cyanobacterium. The functional difference however is that kinase activity is not compulsory for ethylene binding in plants, but is the key role of SynEtr1.

Signal transduction

Two proteins are crucial for interacting ethylene with the gasoreceptors, namely constitutive triple response 1 (CTR1) and ethylene insensitive 2 (EIN2). CTR1 is a serine/threonine protein kinase that functions as a negative regulator of ethylene signalling. It is a member of the signaling protein mitogen-activated protein kinase (MAPK) kinase kinase. EIN2 is required for ethylene signalling and is part of the NRAMP ( natural resistance-associated macrophage protein) family of metal transporters; it comprises a large, N-terminal portion containing multiple transmembrane domains (EIN2-N) in the ER membrane and a cytosolic C-terminal portion (EIN2-C). Other proteins such as reversion to ethylene sensitivity 1 (RTE1),

cytochrome b5 Cytochromes ''b''5 are ubiquitous electron transport hemoproteins found in animals, plants, fungi and purple bacteria, purple phototrophic bacteria. The microsome, microsomal and mitochondrial variants are membrane-bound, while bacterial and tho ...

and tetratricopeptide repeat protein 1 (TRP1) also play important roles in ethylene signaling. RTE1 is a highly conserved proteins in plants and protists but absent in fungi and prokaryotes. TRP1 is genetically related to transmembrane and coiled-coil protein 1 (TCC1) in animals that is involved

F actin Actin is a family of globular multi-functional proteins that form microfilaments in the cytoskeleton, and the thin filaments in muscle fibrils. It is found in essentially all eukaryotic cells, where it may be present at a concentration of over ...

function and competes with Raf-1 for Ras binding. Unlike in most signal transductions where the

ligands In coordination chemistry, a ligand is an ion or molecule with a functional group that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's ...

activate their gasoreceptors to relay their signals, ethylene acts as the suppressor of its gasoreceptor, and the gasoreceptor being the negative regulator in ethylene responses. Ethylene gasoreceptor is active in the absence of ethylene. Without ethylene, the gasoreceptor binds to CTR1 at its C-terminal kinase domain. The kinase activity of CTR1 becomes activated and

phosphorylates In biochemistry, phosphorylation is described as the "transfer of a phosphate group" from a donor to an acceptor. A common phosphorylating agent (phosphate donor) is ATP and a common family of acceptor are alcohols: : This equation can be writt ...

the neighbouring EIN2. As long as EIN2 remains highly phosphorylated, it remains inactive and there never is an ethylene signal relay. In ETR1, the gasoreceptor histidine kinase is required for binding with EIN2. RTE1 can bind to and activate ETR1 independent of CTR1. There is evidence that cytochrome b5 aids or acts similar to RTE1. Ethylene binding to the gasoreceptor disrupts the EIN2 phosphorylation. It does not cause any particular change in the structural feature of the gasoreceptor-CTR1-EIN2 complex or stop the phosphorylation. In fact, at low level of ethylene there is increased gasoreceptor-CTR1-EIN2 complexes, which is then reduced as ethylene level rises. The turnover process is not yet fully understood. The only consequence of ethylene binding is reduced phosphorylation of EIN2. Under such condition EIN2 is activated and is cleaved to release EIN2-C from the membrane-bound EIN2-N portion. The enzyme that causes the cleavage is yet unknown. The role of EIN2-N is also unknown in ''A. thaliana''. But in rice, its homologue OsEIN2-N (Os for ''

Oryza sativa ''Oryza sativa'', having the common name Asian cultivated rice, is the much more common of the two rice species cultivated as a cereal, the other species being ''Oryza glaberrima, O. glaberrima'', African rice. It was History of rice cultivation ...

'', the scientific name for rice) interacts with another protein, mao huzi 3 (MHZ3), a mutation of which gives rise to insensitivity to ethylene. EIN2-C is the main component that mediates ethylene signal in the cell. It acts in two ways. In one, it binds the mRNAs that encode for EIN3-binding F-box proteins, EBF1 and EBF2 to cause their

degradation Degradation may refer to: Science * Degradation (geology), lowering of a fluvial surface by erosion * Degradation (telecommunications), of an electronic signal * Biodegradation of organic substances by living organisms * Environmental degradation ...

. In another, it enters the nucleus to bind with EIN2 nuclear associated protein 1 (ENAP1) to regulate

transcriptional Transcription is the process of copying a segment of DNA into RNA for the purpose of gene expression. Some segments of DNA are transcribed into RNA molecules that can encode proteins, called messenger RNA (mRNA). Other segments of DNA are transc ...

and translational activities of EIN3 and the related EIL1 transcription factor to cause most of the ethylene responses.{{Cite journal, last1=Zhang, first1=Weiqiang, last2=Hu, first2=Yingxiong, last3=Liu, first3=Jian, last4=Wang, first4=Hui, last5=Wei, first5=Jihui, last6=Sun, first6=Pingdong, last7=Wu, first7=Lifeng, last8=Zheng, first8=Hongjian, date=2020, title=Progress of ethylene action mechanism and its application on plant type formation in crops, journal=Saudi Journal of Biological Sciences, volume=27, issue=6, pages=1667–1673, doi=10.1016/j.sjbs.2019.12.038, pmc=7253889, pmid=32489309, bibcode=2020SJBS...27.1667Z

References

Signal transduction Plant hormones Gaseous signaling molecules Plant growth regulators Plant physiology