Receptors as binding sites
Cells interact with each other by sending and receiving signals which are sent using a chemical substance. Molecules of the chemical signal are produced by one cell and bind to receptors in another. Receptors are proteins with a site for the signalling chemical bind. Binding causes changes in the receptor which stimulate a response to the signal by the target cell.
A molecule that binds selectively to a specific site on another molecule is known as a ligand. The site on a receptor to which the signalling chemical binds is called the ligand-binding site.
Compare contrast enzymes and receptors
The similarities between receptors and enzymes in their binding is:
- In both enzymes and receptors binding of the Ligand occurs at a specific site.
- The shape and chemical properties of the binding site match those of the ligand preventing other substances from binding.
-Both enzymes and receptors are unchanged by the binding of a ligand/substrate even if there are temporary changes to induce fit.
The differences however, are:
- When a substrate binds to the active site of an enzyme the substrate changes and is converted chemically into a product and released. Another substrate can then bind to the active site and the cycle can repeat many times per second as binding is very brief.
-On the other hand a signalling chemical may remain bound to a receptor for a long time and it does not convert the chemical signal into a product. The signalling chemical is eventually released unchanged.
Quorum sensing
A numerical count decides if there is a quorum, quorum sensing is an intercellular communication between organisms like bacteria to assess whether a population is large enough for a group activity. If the population density rises above a certain threshold a switch and activity or behaviour will be triggered.
In quorum sensing signalling molecules are secreted at a low rate by all cells in the population. These molecules diffuse freely between cells and bind to receptors in each cell. When there has been sufficient binding of a signalling molecules to a receptor and cells gene expression is changed and that causes a switch in activities.
Quorum sensing as an example of interaction signalling molecules pass from cell to cell and the activities promoted by quorum sensing are examples of interdependence they are only effective if more than one cell participates .
Bioluminescence as an example of quorum sensing
V.fischeri cells produce and secrete a type of signalling molecule known as an auto inducer. The auto inducer can diffuse between cells and binds to a receptor protein in the cytoplasm known as LuxR. When the binding has occurred the LuxR-autoinducer complex binds to the DNA of the bacteria at a position where it induces the transcription of genes. Expression of these chains result in the product of the enzyme Luciferase. Luciferase catalyses and oxidation reaction that releases energy which is transformed into a greenish blue light leading to bioluminescence.
Is bioluminescence can allow for the bacteria to form a mutualistic relationship with various animal hosts such as the bobtail squid. With the squid, the bacteria colonise structure called a light organ which allows the squid to camouflage in moonlight.
Hormones
Hormones are signalling chemicals produced in small amounts by groups of specialised cells in the body and they are transported by the bloodstream. Organs that are specialised for secretion are called glands. Most hormones are secreted into blood capillaries in the gland tissue. Because of this internal secretion, glands that secrete hormones are called endocrine glands. Exocrine glands have a duct leading out of the organ to transport the secretion.
The bloodstream transports hormones to all parts of the body. However, they only have effects on target cells which have receptors for the hormone. The hormone regulates the activities of the target cell by promoting or inhibiting specific processes. Activities of a target cell can be affected for much longer than with nerve impulses since hormones persist in the body longer. One hormone can have very widespread effects because of the transport in the bloodstream.
Examples of hormones are insulin thyroxine, and testosterone.
Neurotransmitters
Neurotransmitters are chemicals that transmit signals across synapses. A synapse is a junction between two neurons in the nervous system: the synaptic neuron secretes the neurotransmitter and the postsynaptic neuron receives it. The neurotransmitter is secreted when a nerve impulse reaches the end of the pre-synaptic neuron. It diffuses across the gap between the two neurons and then binds to receptors in the plasma membrane of the post synaptic neuron. Executory neurotransmitters stimulate nerve impulses, inhibitory neurotransmitters have the opposite effect.
The gap between two neurons at the synapse is between 20 to 40 nm and most neurotransmitters only travel this very short distance, neuro transmitters therefore conveyor signal far more quickly than hormones. Your transmitters are rapidly broken down in the synaptic gap or absorbed into the pre-synaptic neuron so they only persist for a fraction of a second, this rapid removal of neurotransmitters from the synaptic gap ensures that they only affect one specific post synaptic neuron and don’t diffuse out into the synapses of other neurons causing more widespread effects.
Cytokines
Cytokines are small proteins that act as a signalling chemical they are secreted by a wide range of cells. The same cytokinin may be secreted by different cell types and one cell type may secrete several different cytokines. Certain cytokines can be secreted by almost all cells in the body. Cytokines are not usually transported as far as hormones. Instead they act either on the cell that produce them or on a nearby cell. Cytokines cannot enter cells so they bind the receptors in the plasma membrane of a target cell. The binding causes cascades of signalling inside the cell Leading to changes in gene expression and therefore changes in cell activity. One type of cytokinin can easily bind to several types of receptors so they have multiple effects.
Cytokines have cell signalling rules in inflammation and other responses of the immune system. They also have roles in the control of cell gross and proliferation in the development of embryos.
Erythropoietin, interferon and interleukin are example examples of cytokines
Calcium ions
Calcium ions are used for cell signalling in both muscle fibres and neurons. In muscle fibres calcium ions are pumped into a specialised form of endoplasmic reticulum called the sarcoplasmic reticulum which generates a high concentration. When the muscle fibres receives a muscle impulse calcium channels open in the membrane of the sarcoplasmic reticulum the ions can diffuse out. They bind to proteins that block muscle contraction causing the proteins to change position and allow for muscle contraction to occur. Some muscle fibroid does not receive more nerve pulses. These changes are reversed and the calcium is pumped back into the sarcoplasmic reticulum.
In neurons the arrival of a nerve impulse at a pre-synaptic membrane causes calcium channels to open, allowing inward diffusion. Inside the synaptic neuron calcium ions cause secretion of neurotransmitters into the synaptic gap by exocytosis. The calcium ions are rapidly pumped back out into the synaptic cleft.
Hormones and neurotransmitters
Signalling systems using hormones and neurotransmitters have evolved repeatedly and a wide range of chemical substances have become signalling chemicals. A signalling chemical has to:
-Have a distinctive shape and chemical properties so the receptor can distinguish between it and other chemicals
-Be small and soluble enough to be transported
Some examples of hormones are as follows :
Amines:
-Melatonin
-Thyroxine
-Epinephrine
peptides:
-Insulin
-Glucagon
-ADH
steroids:
-oestradiol
-Progesterone
-Testosterone
Examples of neurotransmitters are :
amines:
-Dopamine
-norepinephrine
gases:
-Nitrous oxide
amino acids:
-Glutamate
-Glycine
esters
-Acetylcholine
Localised and distant effects of signalling molecules
Some signalling molecules are only transported a very short distance and therefore have very localised effects. For example neurotransmitters are released by pre-synaptic neurons and may only have to diffuse 20 nm to reach one postsynaptic neuron that they affect.
Other signalling molecules are transported long distances in the body from the cell that secretes them to the target cells. Hormones are transported in the blood from the gland that produces them to all parts of the body. The target cells could be in any part of the body. For example, the luteinzing hormone is secreted by the pituitary gland adjacent to the brain. In males the target cells of LH are in the testes and females they are in the ovaries, so the effects of the hormone are very distant from its source.
Differences between transmembrane receptors and intracellular receptors
Signalling chemicals can be divided into two groups, according to whether they enter the target cell or not. Receptors for signalling chemicals that do pass through the plasma membrane are located in the cytoplasm or nucleus of the cell and they are intracellular. Receptors for chemicals that do not penetrate are located in the plasma membrane of the target cell with the binding site exposed to the exterior. These receptors extend across the membrane with a region extending into the cytoplasm and they are called transmembrane receptors.
The location of receptors is determined by the distribution of hydrophilic and hydrophobic amino acids on the surface of the receptor protein.
-Intracellular receptors have hydrophilic amino acids so they remain dissolved in the aqueous fluids of the cytoplasm or nucleus.
-Trans membrane receptors have a band of hydrophobic amino acids on their surface that is attracted to the polar tales of phospholipids in the core of the membrane. On either side of the band there are hydrophilic amino acids which are in contact with the acquiesce solutions inside and outside the cell.
Initiation of signalling transduction pathways by receptors
Binding of a signalling chemical to a receptor causes a sequence of interactions in the cell called a signal transduction pathway. These pathways are very varied as they have evolved repeatedly rather than having a common origin. Some signalling chemicals such as proteins cannot pass through the plasma membrane instead they bind to receptors in the plasma membrane. Other signalling chemicals for example steroids pass through the membrane and bind to the intracellular receptors. Transmembrane and intracellular receptors use different transduction pathways.
When a signalling chemical binds to the outer side of a transmembrane receptor, it changes the structure of the receptor. The inner side of the receptor becomes catalytically active and causes production of a secondary messenger within the cell. This conveys the signal to factors within the cell that carry out the responses.
Finding of signalling chemicals to intracellular receptors results in the formation of an active ligand-receptor complex. In most cases, this complex regulates gene expression by binding to DNA at specific sites promoting or inhibiting the transcription of particular genes.
Trans membrane receptors for neurotransmitters and changes to membrane potential
Neurotransmitters convey signals between neurons, and between neurons and muscle. Neurotransmitters are released into the synaptic gap and diffuse to the membrane of the postsynaptic neuron or the muscle fibre. There, they bind to receptors in these membranes. The receptors are trans membrane proteins. Binding causes membrane channels to open an ions move through these channels by facilitated diffusion, changing the membrane potential. This change in potential is a signal that stimulates or inhibits either a nerve impulse in a postsynaptic neuron, or a contraction in a muscle fibre.
Acetylcholine is used as a neurotransmitter in many synopsis, including those between a neuron and muscle fibres. When acetylcholine binds to the binding site on an acetylcholine receptor, there is a confirmational change on said receptor. A channel opens allowing sodium ions to pass into the cell. This leads to a local depolarisation that triggers an action potential.
Transmembrane receptors that activate G protein
G protein coupled receptors are a large and diverse group of trans membrane receptors. They convey signals into cells using a second protein located in the plasma membrane which is called G protein. The three subunits of G protein; alpha beta and gamma, assemble on the receptor. A molecule of guanosine diphosphate (GDP) bound to the alpha sub unit keeps the G protein in an inactive state.
When a ligan binds to the binding site on the receptor the receptor changes shape. This causes changes in the couple G protein, so the GDP detach from the alpha sub unit. This allows guanosine triphosphate to bind in its place. Binding of GTP activates the G protein, which separates into its sub units and disassociates from the receptor. The activated G protein subunits caused further changes within the cell, triggering the cells response to the signal brought by the ligand.
Mechanism of action of epinephrine receptors
Epinephrine binds to a trans membrane receptor in the plasma membrane of target cells. This changes the shape of the receptor, activating G protein within the membrane. Activated G protein activates the enzyme adenyl cyclase in the membrane and this converts ATP in the cytoplasm into cyclic AMP. cAMP is the second or secondary messenger. Secondary messengers start a sequence of responses within the cell, amplifying the signal until the large scale process is triggered. This happens very rapidly.
Transmembrane receptors with tryosine kinase activity
A kinase is an enzyme that adds a phosphate group from ATP to a specific molecule. This process is called phosphorylation. For example, the enzyme tyrosine kinase can transfer phosphate from ATP to the amino acid tyrosine into a protein.
The insulin receptor is a transmembrane protein that is activated by the binding of insulin. The two tails of the protein that extend into the cytoplasm are tyrosine kinase enzymes. The binding of insulin causes structural changes in the receptor so the two tails connect to form a dimmer. Then each tail phosphorylises the other tail. These changes trigger a biochemical chain of events inside the cell. Vesicles containing glucose transporters move to the plasma membrane and fuse with it. Inserting transporters into the membrane. These transporters are channel proteins that allow glucose enter the cell by facilitated diffusion. The glucose can then be used as a substrate and cell respiration.
Intracellular receptors that affect gene expression
Steroid hormones are hydrophobic which means they are soluble and lipids and are able to pass through the membrane. Once inside the cell they bind to receptors in the cytoplasm. The hormone receptor complex enters the nucleus and attaches to the DNA. This activates the production of a particular polypeptide for example, the antiandrogen receptors binds to testosterone and the resulting complex increases production of the FADS1 gene. This intern increases production of important fats in prostate cells.
Effects of the hormone oestradiol and progesterone on target cells
The hormones oestradiol and progesterone are involved in reproduction.
Oestradiol has a broad range of effects in the ovary and the uterus. It also acts on the brain helping to regulate and release reproductive hormones. Within the hypothalamus of the brain, the hormone gonadotropin releasing hormone (GnRH) is produced and released. This hormone triggers the release of the sex hormones, luteinzing hormone (LH) and follicle stimulating hormone (FSH) from the anterior pituitary. A different stages of the human menstrual cycle stray can either inhibit or promote the release of GNRH by the hypothalamus. Just before and during ovulation radial has a stimulating effect by binding to a receptor within the cytoplasm of the hypothalamus cell. Once bound, the hormone receptor complex moves to the nucleus where it acts as a transcription factor, enhancing the transcription of GNRH mRNA.
The hormone progesterone is produced by the ovary and maintains the uterine lining so that it can support a developing fetus. Progesterone is a steroid hormone, able to diffuse directly through the plasma membrane of uterine cells and it binds to receptor in the cytoplasm. The hormone receptor complex then enters the nucleus where it interacts with DNA as a transcription factor. This affects gene expression for example, one of the genes activated is an insulin like growth factor which contributes to the cellular proliferation necessary for maintaining the lining of the endometrium.
Regulation of cell signalling pathways by positive and negative feedback
In a positive feedback process, the end product of a pathway amplifies the starting point so that more product is created. For example, in muscle, the endoplasmic reticulum stores calcium. The binding of an inositiol triphosphate (IP3) molecule to an IP3 receptor causes the partial release of calcium from the endoplasmic reticulum. This increase in calcium ions activates the IP3 receptor on a neighbouring calcium channel causing further increase in calcium ions. This process is known as calcium induced calcium release.
In a negative feedback process and increase in the end product of a pathway shuts off the start of the pathway. In other words, the end product inhibit its own production. For example, testosterone production is regulated by negative feedback. GNRH released by the hypothalamus act on the hypothalamus stimulating the release of LH. LH stimulates the release of testosterone from leydig cells in the testes. Increasing testosterone levels have two effects:
-Signals to the anterior pituitary decrease the release of LH
-Signals to the hypothalamus stop the release of GNRH
