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Cell communication - Coggle Diagram
Cell communication
9.1 Signaling Molecules and Cellular Receptors
Two types of cell communication
intercellular signaling
: between cells
intracellular signaling
: communication within a cell
Chemical signals are released by
signaling cells
in the form of small, usually volatile or soluble molecules called
ligands
.
A
ligand
is a molecule that binds another specific molecule, in some cases, delivering a signal in the process.
Ligands can thus be thought of as signaling molecules.
Ligands interact with proteins in target cells, which are cells that are affected by chemical signals; these proteins are also called receptors.
Ligands and receptors exist in several varieties; however, a specific ligand will have a specific receptor that typically binds only that ligand.
Forms of Signaling
Paracrine Signaling
Signals that act locally between cells that are close together.
Paracrine signals move by diffusion through the extracellular matrix.
These types of signals usually elicit quick responses that last only a short amount of time and they are localized
In order to keep the response localized, paracrine ligand molecules are normally quickly degraded by enzymes or removed by neighboring cells.
Removing the signals will reestablish the concentration gradient for the signal, allowing them to quickly diffuse through the intracellular space if released again.
Endocrine signaling
Signals from distant cells are called endocrine signals, originate from endocrine cells.
These types of signals usually produce a slower response but have a longer-lasting effect.
The ligands released in endocrine signaling are called hormones - signaling molecules that are produced in one part of the body but affect other body regions some distance away.
Hormones travel the large distances between endocrine cells and their target cells via the bloodstream, which is a relatively slow way to move throughout the body.
Because of their form of transport, hormones get diluted and are present in low concentrations when they act on their target cells. This is different from paracrine signaling, in which local concentrations of ligands can be very high.
Autocrine Signaling
Short distance
produced by signaling cells that can also bind to the ligand that is released
the signaling cell and the target cell can be the same or a similar cell
often occurs during the early development of an organism to ensure that cells develop into the correct tissues and take on the proper function.
Autocrine signaling also regulates pain sensation and inflammatory responses.
Further, if a cell is infected with a virus, the cell can signal itself to undergo programmed cell death, killing the virus in the process.
In some cases, neighboring cells of the same type are also influenced by the released ligand.
In embryological development, this process of stimulating a group of neighboring cells may help to direct the differentiation of identical cells into the same cell type, thus ensuring the proper developmental outcome.
Direct Signaling Across Gap Junctions
connections between the plasma membranes of neighboring cells
intracellular mediators: water-filled channels allow small signaling molecules to diffuse between the two cells.
The specificity of the channels ensures that the cells remain independent but can quickly and easily transmit signals. .
The transfer of signaling molecules communicates the current state of the cell that is directly next to the target cell; allows a group of cells to coordinate their response to a signal that only one of them may have received.
In plants, plasmodesmata are ubiquitous, making the entire plant into a giant, communication network
Types of Receptors
Internal receptors
found in the cytoplasm of the cell
respond to hydrophobic ligand molecules that are able to travel across the plasma membrane
Once inside the cell, many of these molecules bind to proteins that act as regulators of mRNA synthesis (transcription) to mediate gene expression
Gene expression
the cellular process of transforming the information in a cell's DNA into a sequence of amino acids -> forms a protein.
When the ligand binds to the internal receptor, a conformational change is triggered that exposes a DNA-binding site on the protein.
The ligand-receptor complex moves into the nucleus, then binds to specific regulatory regions of the chromosomal DNA and promotes the initiation of transcription
Transcription
the process of copying the information in a cells DNA into a special form of RNA called messenger RNA (mRNA)
the cell uses information in the mRNA (which moves out into the cytoplasm and associates with ribosomes) to link specific amino acids in the correct order, producing a protein.
Internal receptors can directly influence gene expression without having to pass the signal on to other receptors or messengers.
Cell-Surface Receptors
cell surface, membrane-anchored (integral) proteins that bind to external ligand molecules.
spans the plasma membrane and performs signal transduction, in which an extracellular signal is converted into an intercellular signal
Ligands that interact with cell-surface receptors do not have to enter the cell that they affect
cell-specific proteins or markers because they are specific to individual cell types.
a malfunction in any one of these proteins could have severe consequences.
Errors in the protein structures of certain receptor molecules have been shown to play a role in hypertension (high blood pressure), asthma, heart disease, and cancer.
Components
an external ligand-binding domain,
a hydrophobic membrane-spanning region
an intracellular domain inside the cell.
The ligand-binding domain is also called the extracellular domain. The size and extent of each of these domains vary widely, depending on the type of receptor.
involved in most of the signaling in multicellular organisms
G-protein-linked receptors
Ion channel-linked receptors
Signaling Molecules
Produced by signaling cells and the subsequent binding to receptors in target cells
ligands act as chemical signals that travel to the target cells to coordinate responses
Small Hydrophobic Ligands
directly diffuse through the plasma membrane and interact with internal receptors.
Important members of this class of ligands are the steroid hormones
lipids that have a hydrocarbon skeleton with four fused rings;
different steroids have different functional groups attached to the carbon skeleton
sex hormone, estradiol, which is a type of estrogen; the male sex hormone, testosterone; and cholestero
Other hydrophobic hormones include thyroid hormones and vitamin D.
hydrophobic ligands must bind to carrier proteins while they are being transported through the bloodstream in other to be stored in blood.
Water-Soluble Ligands
polar and therefore cannot pass through the plasma membrane unaided
sometimes too large to pass through the membrane at all
quite diverse and includes small molecules, peptides, and proteins.
Other Ligands
Nitric oxide
interact with receptors in smooth muscle and induce relaxation of the tissue
short half-life -> only functions over short distances
Nitroglycerin, a treatment for heart disease, acts by triggering the release of NO, which causes blood vessels to dilate (expand), thus restoring blood flow to the heart.
9.3 Response to the Signal
Gene Expression
[
An
inhibitor
is a molecule that binds to a protein and prevents it from functioning or reduces its function
PKC can interact is a protein that acts as an inhibitor
In this case, the effect of phosphorylation is to inactivate an inhibitor and thereby activate the process of transcription.
When Iκ-B is bound to NF-κB, the complex cannot enter the nucleus of the cell, but when Iκ-B is phosphorylated by PKC, it can no longer bind NF-κB, and NF-κB (a transcription factor) can enter the nucleus and initiate RNA transcription
the inhibitor is a protein called Iκ-B, which binds to the regulatory protein NF-κB.
MAP kinase ERK
ERK is activated in a phosphorylation cascade when epidermal growth factor (EGF) binds the EGF receptor (see Figure 9.10). Upon phosphorylation, ERK enters the nucleus and activates a protein kinase that, in turn, regulates protein translation ( Figure 9.14).
Some signal transduction pathways regulate the transcription of RNA. Others regulate the translation of proteins from mRNA.
Increase in Cellular Metabolism
affects muscle cells
The activation of β-adrenergic receptors in muscle cells by adrenaline leads to an increase in cyclic AMP (cAMP) inside the cell
Also known as epinephrine, adrenaline is a hormone (produced by the adrenal gland attached to the kidney) that readies the body for short-term emergencies
Cyclic AMP activates PKA (protein kinase A), which in turn phosphorylates two enzymes
The first enzyme promotes the degradation of glycogen by activating intermediate glycogen phosphorylase kinase (GPK) that in turn activates glycogen phosphorylase (GP) that catabolizes glycogen into glucose
Phosphorylation of the second enzyme, glycogen synthase (GS), inhibits its ability to form glycogen from glucose
In this manner, a muscle cell obtains a ready pool of glucose by activating its formation via glycogen degradation and by inhibiting the use of glucose to form glycogen, thus preventing a futile cycle of glycogen degradation and synthesis
The glucose is then available for use by the muscle cell in response to a sudden surge of adrenaline—the “fight or flight” reflex.
Cell Growth
The ligands that promote cell growth are called
growth factors
Most growth factors bind to cell-surface receptors that are linked to tyrosine kinases receptor tyrosine kinases (RTKs)
Activation of RTKs initiates a signaling pathway that includes a G-protein called RAS, which activates the MAP kinase pathway described earlier.
The enzyme MAP kinase then stimulates the expression of proteins that interact with other cellular components to initiate cell division.
Cell Death - Apoptosis
allows a cell to die in a controlled manner that prevents the release of potentially damaging molecules from inside the cell
There are many internal checkpoints that monitor a cell’s health; if abnormalities are observed, a cell can spontaneously initiate the process of apoptosis.
However, in some cases, such as a viral infection or uncontrolled cell division, the cell’s normal checks and balances fail
External signaling can also initiate apoptosis
For example, most normal animal cells have receptors that interact with the extracellular matrix, a network of glycoproteins that provides structural support for cells in an organism
The binding of cellular receptors to the extracellular matrix initiates a signaling cascade within the cell
However, if the cell moves away from the extracellular matrix, the signaling ceases, and the cell undergoes apoptosis.
This system keeps cells from traveling through the body and proliferating out of control.
Another example of external signaling that leads to apoptosis occurs in T-cell development
T-cells are immune cells that bind to foreign macromolecules and particles, and target them for destruction by the immune system
Normally, T-cells do not target “self” proteins (those of their own organism), a process that can lead to autoimmune diseases
In order to develop the ability to discriminate between self and non-self, immature T-cells undergo screening to determine whether they bind to so-called self proteins
If the T-cell receptor binds to self proteins, the cell initiates apoptosis to remove the potentially dangerous cell.
Apoptosis is also essential for normal embryological development
In vertebrates, for example, early stages of development include the formation of web-like tissue between individual fingers and toes
A cell signaling mechanism triggers apoptosis, which destroys the cells between the developing digits.
Termination of the Signal Cascade
The aberrant signaling often seen in tumor cells is proof that the termination of a signal at the appropriate time can be just as important as the initiation of a signal
One method of stopping a specific signal is to degrade the ligand or remove it so that it can no longer access its receptor
One reason that hydrophobic hormones like estrogen and testosterone trigger long-lasting events is because they bind carrier proteins
These proteins allow the insoluble molecules to be soluble in blood, but they also protect the hormones from degradation by circulating enzymes
many different enzymes reverse the cellular modifications that result from signaling cascades
phosphatases are enzymes that remove the phosphate group attached to proteins by kinases in a process called dephosphorylation
Cyclic AMP (cAMP) is degraded into AMP by phosphodiesterase, and the release of calcium stores is reversed by the Ca2+ pumps that are located in the external and internal membranes of the cell.
9.2 Propagation of the Signal
Overview
Signal transduction
only occurs with cell-surface receptors because internal receptors are able to interact directly with DNA in the nucleus to initiate protein synthesis
Continuation of a signal once a ligand binds to a receptor, the signal is transmitted through the membrane and into the cytoplasm is called signal transduction
When a ligand binds to its receptor, conformational changes occur can propagate through the membrane region of the receptor and lead to activation of the intracellular domain or its associated proteins
In some cases, binding of the ligand causes
dimerization
of the receptor, which means that two receptors bind to each other to form a stable complex called a
diner
- a chemical compound formed when two molecules (often identical) join togethe
The binding of the receptors in this manner enables their intracellular domains to come into close contact and activate each other.
Binding Initiates a Signaling Pathway
After the ligand binds to the cell-surface receptor, the activation of the receptor’s intracellular components sets off a chain of events that is called a signaling pathway/ cascade
In a signaling pathway, second messengers, enzymes, and activated proteins interact with specific proteins - are in turn activated in a chain reaction that eventually leads to a change in the cell’s environment
Signaling pathways can get very complicated very quickly because most cellular proteins can affect different downstream events, depending on the conditions within the cell
A single pathway can branch off toward different endpoints based on the interplay between two or more signaling pathways, and the same ligands are often used to initiate different signals in different cell types.
signal integration
of the pathways, in which signals from two or more different cell-surface receptors merge to activate the same response in the cell
ensure that multiple external requirements are met before a cell commits to a specific response.
The effects of extracellular signals can also be amplified by enzymatic cascades. At the initiation of the signal, a single ligand binds to a single receptor. However, activation of a receptor-linked enzyme can activate many copies of a component of the signaling cascade, which amplifies the signal.
Methods of Intracellular Signaling
Phosphorylation
addition of a phosphate group (PO4–3) to a molecule such as a protein
catalyzed by an enzyme called a kinase
Phosphorylation of serine and threonine residues often activates enzymes
Phosphorylation of tyrosine residues can either affect the activity of an enzyme or create a binding site that interacts with downstream components in the signaling cascade
dephosphorylation by a phosphatase, will reverse the effect.
Second Messengers
small molecules that propagate a signal after it has been initiated by the binding of the signaling molecule to the receptor
help to spread a signal through the cytoplasm by altering the behavior of certain cellular proteins.
Calcium ion
The free concentration of calcium ions (Ca2+) within a cell is very low because ion pumps in the plasma membrane continuously use adenosine-5'-triphosphate (ATP) to remove it
For signaling purposes, Ca2+ is stored in cytoplasmic vesicles, such as the endoplasmic reticulum, or accessed from outside the cell
When signaling occurs, ligand-gated calcium ion channels allow the higher levels of Ca2+ that are present outside the cell (or in intracellular storage compartments) to flow into the cytoplasm, which raises the concentration of cytoplasmic Ca2+
The response to the increase in Ca2+ varies, depending on the cell type involved. For example, in the β-cells of the pancreas, Ca2+ signaling leads to the release of insulin, and in muscle cells, an increase in Ca2+ leads to muscle contractions.
cyclic AMP (cAMP)
Cyclic AMP is synthesized by the enzyme adenylyl cyclase from ATP
role of cAMP in cells is to bind to and activate an enzyme called
cAMP-dependent kinase (A-kinase).
A-kinase regulates many vital metabolic pathways
It phosphorylates serine and threonine residues of its target proteins, activating them in the process.
A-kinase is found in many different types of cells, and the target proteins in each kind of cell are different. Differences give rise to the variation of the responses to cAMP in different cells.
inositol phospholipids
are lipids that can also be converted into second messengers
are membrane components, they are located near membrane-bound receptors and can easily interact with them
Phosphatidylinositol (PI) is the main phospholipid that plays a role in cellular signaling
Enzymes known as kinases phosphorylate PI to form PI-phosphate (PIP) and PI-bisphosphate (PIP2).
products of the cleavage of PIP2
The enzyme phospholipase C cleaves PIP2 to form diacylglycerol (DAG) and inositol triphosphate (IP3)
Diacylglycerol (DAG) remains in the plasma membrane and activates protein kinase C (PKC), which then phosphorylates serine and threonine residues in its target proteins
IP3 diffuses into the cytoplasm and binds to ligand-gated calcium channels in the endoplasmic reticulum to release Ca2+ that continues the signal cascade.
9.4 Signaling in Single-Celled Organisms
Signaling in Yeast
Yeasts are eukaryotes (fungi), and the components and processes found in yeast signals are similar to those of cell-surface receptor signals in multicellular organisms
Budding yeasts ( Figure 9.16) are able to participate in a process that is similar to sexual reproduction that entails two haploid cells combining to form a diploid cell
In order to find another haploid yeast cell that is prepared to mate, budding yeasts secrete a signaling molecule called
mating factor
When mating factor binds to cell-surface receptors in other yeast cells that are nearby, they stop their normal growth cycles and initiate a cell signaling cascade that includes protein kinases and GTP-binding proteins that are similar to G-proteins.
Signaling in Bacteria
Signaling in bacteria enables bacteria to monitor extracellular conditions, ensure that there are sufficient amounts of nutrients, and ensure that hazardous situations are avoided
Quorum sensing
When the population density of the bacteria reaches a certain level, specific gene expression is initiated, and the bacteria produce bioluminescent proteins that emit light
Because the number of cells present in the environment (cell density) is the determining factor for signaling, bacterial signaling was named quorum sensing
Quorum sensing uses
autoinducers
as signaling molecules
Autoinducers are signaling molecules secreted by bacteria to communicate with other bacteria of the same kind
The secreted autoinducers can be small, hydrophobic molecules such as acyl-homoserine lactone (AHL) or larger peptide-based molecules and they have different mode of action
When AHL enters target bacteria, it binds to transcription factors, which then switch gene expression on or off
The peptide autoinducers stimulate more complicated signaling pathways that include bacterial kinases.
The changes in bacteria following exposure to autoinducers can be quite extensive
The pathogenic bacterium Pseudomonas aeruginosa has 616 different genes that respond to autoinducers.
Some species of bacteria that use quorum sensing form biofilms, complex colonies of bacteria (often containing several species) that exchange chemical signals to coordinate the release of toxins that will attack the host
Bacterial biofilms ( Figure 9.18) can sometimes be found on medical equipment
when biofilms invade implants such as hip or knee replacements or heart pacemakers, they can cause life-threatening infections.
The ability of certain bacteria to form biofilms has evolved because of a selection of genes that enable cell-cell communication confers an evolutionary advantage
When bacterial colonies form biofilms, they create barriers that prevent toxins and antibacterial drugs from affecting the population living in the biofilm
As a result, these populations are more likely to survive, even in the presence of antibacterial agents
This often means that bacteria living in biofilms have higher fitness than bacteria living on their own.