Secondary messengers
1. Introduction:
Multicellular organisms cannot survive without efficient communication among cells,
tissues and organs. Regulation and coordination of metabolism, growth, morphogenesis
depends of chemical signals from one part of the plant to another. German botanist
Julius von Sachs is credited for originating this idea in the late nineteenth century [1].
Typically the end result of any signaling pathway is alteration in gene expression via
regulating the transcription factors. Signal transduction pathways often involve the
generation of second messengers, transient secondary signals inside the cell that
greatly amplify the original signal. Binding to a receptor initiates a signal transduction
pathway, often involving the generation of second messengers, such as cyclic
nucleotides, inositol trisphosphate, and calcium, Such pathways normally lead to
changes in gene expression. Chemical signals specifically bind protein receptors found
either on the plasma membrane or in the cell’s cytoplasm [2].
Second messengers are molecules that relay signals received at receptors on the cell
surface such as the arrival of protein hormones, growth factors, etc. to target molecules
in the cytosol and/or nucleus. In addition to their job as relay molecules, second
messengers serve to greatly amplify the strength of the signal. Binding of a ligand to a
single receptor at the cell surface may end up causing massive changes in the
biochemical activities within the cell.
There are 3 major classes of second messengers:
1. cyclic nucleotides (e.g., cAMP and cGMP)
2. inositol trisphosphate (IP3) and diacylglycerol (DAG)
3. calcium ions (Ca2+)
There are three basic types of secondary messenger molecules:
Hydrophobic molecules: water-insoluble molecules such as diacylglycerol,
and phosphatidylinositols, which are membrane-associated and diffuse from
the plasma membrane into the intermembrane space where they can reach and
regulate membrane-associated effector proteins.
Hydrophilic molecules: water-soluble molecules, such as cAMP, cGMP, IP3,
and Ca2+, that are located within the cytosol.
Gases: nitric oxide (NO), carbon monoxide (CO) and hydrogen sulfide (H2S) which
can diffuse both through cytosol and across cellular membranes.
These intracellular messengers have some properties in common:
They can be synthesized/released and broken down again in specific reactions
by enzymes or ion channels.
Some (such as Ca2+) can be stored in special organelles and quickly released when
needed.
Their production/release and destruction can be localized, enabling the cell to limit
space and time of signal activity.
2. Secondary messengers
2.1 3′,5′-cyclic AMP (cAMP)
Adenosine 3':5'-monophosphate, commonly known as cAMP, is a key second
messenger in living organisms ranging from Dictyostelium to Homo sapiens. cAMP was
first described as a regulator of glycogen breakdown in the liver and is now known to be
a second messenger for a wide variety of cellular responses in animals.
2.2 3′,5′-cyclic GMP (cGMP)
It has been shown that the second messenger cyclic guanosine 3,5-monophosphate
(cGMP) is an important signalling component with multiple biological functions in plants
similar to the situation in animals. In plants, there is some biochemical evidence
supporting the existence of plant cGMP-responsive kinases (Newton and Smith, 2004),
and the Arabidopsis genome contains sequences that encode gene products with both
a cyclic nucleotidebinding domain and a protein kinase (Meier and Gehring, 2006).
However, specific cGMP targets in plants are largely unknown and in particular there is
little molecular evidence available of bonafide cGMP-dependent kinases.
2.3 Nitric oxide (NO)
Nitric Oxide has multifunctional roles in plants: stomatal movement, host-pathogen
interactions, hormonal signaling during growth/development and adaptation to
abiotic/biotic stress. NO in guard cells plays a very important role as a secondary
messenger during stomatal closure induced by effectors.
2.4 Cyclic ADP-ribose (cADPR)
There is wide range of physiological functions are signalled and regulated by
mobilization of intracellular Ca2+ stores. The generally accepted view is that cells
possess multiple types of stores that can be mobilized by specific messenger
molecules. Two unrelated nucleotides with Ca2_-mobilizing activity was identified viz.
cyclic ADP-ribose (cADPR) and nicotinic acid adenine dinucleotide phosphate
(NAADP). The action of cADPR on the channel is temperature-dependent, and
proposed to be as a temperature sensing mechanism in cells.
2.5 1,2-diacylglycerol (DAG)
Diacylglycerol (DAG) has unique functions as a basic component of membranes, an
intermediate in lipid metabolism and a key element in lipid-mediated signaling.
2.6 Inositol trisphosphate (IP3)-
Inositol trisphosphate or inositol 1,4,5-trisphosphate (also commonly known as
triphosphoinositol; abbreviated InsP3 or Ins3P or IP3), together with diacylglycerol
(DAG), is a secondary messenger molecule used in signal transduction and lipid
signaling in biological cells. While DAG stays inside the membrane, IP3 is soluble and
diffuses through the cell. It is made by hydrolysis of phosphatidylinositol 4,5-
bisphosphate (PIP2), a phospholipid that is located in the plasma membrane, by
phospholipase C (PLC).
Increases in the intracellular Ca2+ concentrations are often a result of IP3 activation.
When a ligand binds to a G protein-coupled receptor (GPCR) that is coupled to a Gq
heterotrimeric G protein, the α-subunit of Gq can bind to and induce activity in the PLC
isozyme PLC-β, which results in the cleavage of PIP2 into IP3 and DAG.[10]
If a receptor tyrosine kinase (RTK) is involved in activating the pathway, the isozyme
PLC-γ has tyrosine residues that can become phosphorylated upon activation of an
RTK, and this will activate PLC-γ and allow it to cleave PIP2 into DAG and IP3. This
occurs in cells that are capable of responding to growth factors such as insulin, because
the growth factors are the ligands responsible for activating the RTK.[11]
IP3 (also abbreviated Ins3P) is a soluble molecule and is capable of diffusing through
the cytoplasm to the ER, or the sarcoplasmic reticulum (SR) in the case of muscle cells,
once it has been produced by the action of PLC. Once at the ER, IP3 is able to bind to
the Ins3P receptor (Ins3PR) on a ligand-gated Ca2+ channel that is found on the surface
of the ER. The binding of IP3 (the ligand in this case) to InsP3R triggers the opening of
the Ca2+ channel, and thus release of Ca2+ into the cytoplasm.[11] In heart muscle cells
this increase in Ca2+ activates the ryanodine receptor-operated channel on the SR,
results in further increases in Ca2+ through a process known as calcium-induced
calcium release. IP3 may also activate Ca2+ channels on the cell membrane indirectly,
by increasing the intracellular Ca2+ concentration.
2.7 Ca++
Evolution has adopted positively charged calcium as the primary signaling element of
cells. Ca2+ is one of the principal second messengers for functioning as a central node
in the overall “signaling web” and plays an important role in providing stress tolerance to
plants.
Analysis of [Ca2+ ] in dynamics has demonstrated its signaling role in plant cells in
response to a wide array of environmental cues. In general, the stress leads to
increased cytosolic Ca2+, which initiates the stress signal transduction pathways for the
stress tolerance. Ca2+ is the most tightly regulated ion within all membrane-bound
organisms and binds to several proteins to effect changes in localization, association,
and function. It is now clear that Ca2+ signaling affects almost every aspect of the
cellular metabolism of living organisms.
In fact, an indirect increase in [Ca2+] cyt in plant cells is mediated by the increase in
intracellular concentrations of other second messengers such as cyclic GMP, cyclic
AMP, and IP3, in response to stimuli. The elevation of Ca 2+ concentration in cytoplasm
is found to be a key event in the plant cell for transduction of various signals to a
biological effect [3].
