CELL SIGNALLING

BY: RAHUL ANDHARIA (MSIWM001)

Communication between cells is referred to as cell signalling. Cell signalling is the process through which cells responds to external stimuli. While studying the duct secretion system, Claude Bernard, in 1855 discovered process of cell signalling.

What kinds of signals do cells receive?

• Cells communicate by sending chemical signals.
• Sending cell is the one which sends the signal in form of proteins or other molecules which is received by a target cell.

How do cells recognise signals?

• Cells posses special molecules called receptors which binds to signalling molecules and initiate physiological response.
• For a target cell to detect the signal, it must have a appropriate receptor to bind to.
• Receptor is called a transmembrane protein, which binds to cells and transmits signals.

How do cells respond to signals?

• When a signal is received by a receptor protein, it undergoes conformational changes and leads to series of biochemical reactions.
• Signal transduction cascade( intracellular pathway) than amplify the message producing many intracellular signals from the receptor to which it was originally bound.
• When receptors are activated, it initiates synthesis of second messenger(ligand) which coordinates intracellular pathways.

Example of molecule common second messenger- Cyclic AMP

Three stages of cell signalling:

1. Stage 1 where receptor molecule binds with the signal molecule, called reception stage.
2. Stage 2, in which series of chemical signals results in activation of enzyme molecules, called signal transduction stage.
3. Stage3, resulting cellular responses, which is the response stage.

Forms/types of signalling:

Paracrine signalling:

• Cell signalling to neighbouring cell.
• In this type of signalling, signals are transmitted within relatively shorter distances.
• Allows cells to coordinate locally with neighbour cells.
• They play a role in many tissue and context signalling, but their vital role is during development where they communicate one group of cells to select which type of cellular identity from other group of cells.
• Example- spinal cord development in humans.

Synaptic signalling:

• In synaptic signalling, nerve cells transmit the signal. This kind of signalling is an example of paracrine signalling.
• The name is synaptic, because the signal transduction takes place between Junction of two nerve cells, which is called a synapse.
• When a signal is received by a sending neuron, an electrical impulse is generated in the cell which travels through Axon, a fibre like extension.
• Ligands, called neurotransmitters are released, when impulses reaches synapse.
• Neurotransmitters than, binds to the receptors of the receiving cell, causing chemical changes in the cell.
• Immediately, the sender cell than, degrades the neurotransmitters that are released into the chemical synapse. This way the system resets again, to receive a second signal and this process continues.

Autocrine signalling:

• In autocrine signalling, the cell targets itself, that is cell signals itself. The ligand released will bind to the cell’s own receptors.
• This type off signalling plays many roles, like for example autocrine signalling is involved in development, where it guides cells to take-up it’s correct identity.
• This type of signalling bid also known to play a role in cancer, where it is known to be involved in metastasis ( spread of cancer to other body parts).
• Sometimes, cell simultaneously has both paracrine as well as autocrine effect, so as a result it binds to itself as well as to the sender cell.

Endocrine signalling:

• This type of signalling uses circulatory system as a network to transmit messages for long distances.
• In long distance endocrine signalling, specialized cells produces the signals and releases into blood stream, through which they reach the target cells.
• Here signals are produced and circulated in blood stream via hormones. Hormones carries signal produced in one part of the body to other parts.
• Thyroid glands, pituitary glands, hypothalamus, gonads and pancreas are the endocrine glands that releases hormones.

Example: GH- growth hormone, released by pituitary gland promotes growth of cartilage and skeleton.

Signalling via cell-cell contact:

• Cell-cell contact signalling occurs via Gap junctions. These water filled channels allows intracellular mediators to diffuse between two cells.
• Molecules like DNA and proteins cannot fit through channels without special assistance, but small molecules like ions and water can pass through.
• Transfer of signalling molecules will lead to transfer of current state of one cell to the neighbouring cell. This will allow cells to coordinate the response, which only one of them would have received.
• Two cells carrying compliment protein may bind to each other, resulting in the change of shape of one or both the protein that transmits the signal. This is another type of direct cell signalling which is particularly seen in immune cells, which uses it to recognise its own self cells and pathogen cells.

Types of Receptors involved in signalling:

Intracellular receptors:

• Located in the cytoplasm of cells. It has other two types:
• Nuclear receptors: It has  DNA binding domains. When these are bound to thyroid or steroid hormones, it results in formation of a complex which enters the nucleus and regulates gene transcription.
• IP3 receptors: present in endoplasmic reticulum. It helps in releasing ca2+ ions which are vital for muscle contraction.

Ligand gated ion channel receptors:

• They spann  across the plasma membrane.
• Major function of this receptor is to allow hydrophilic ions to pass the thick fatty membranes of our cells.
• When bound to acetylcholine, a neurotransmitter, ions like k+, ca2+, Na+ and cl- are allowed to flow across the membrane to allow neural firing to take place(transmission of impulse.

G-protein coupled receptors:

• Largest receptors in eukaryotes.
• They are known to be very diverse as they receive input from complex and diverse group of signal ranging from sugars, peptides and light energy.
• Binding of ligand to this receptors results in activation of G-protein, which transmits entire cascade of second messenger signals, which carry out important functions like sight, sensation, growth and inflammation.

Receptor Tyrosine kinases:

• When ligand binds to this receptors, it results in dimerization of tyrosine kinase domains.
• This results in phosphorylation of their tyrosine kinase domains which allows the intracellular proteins to become active by binding to phosphorylated sites.
• One of the major role of this receptors is in growth pathways.

Ligand used in signalling:

• Hydrophobic ligands- binds to intracellular receptors. These have fatty properties and possess steroid hormones and D3 vitamin.
• Hydrophilic ligands- binds directly to cell surface receptors. These are mostly amino acids derived ligands.

Types of signalling molecules:

• Intracrine: produced by target cells and binds to receptors present within the signalling cells.
• Autocrine: they are distinct. They function on target cells as well as they function internally. Example- immune cells of the body.
• Juxtacrine: often called contact-dependant signalling. They generally target adjacent cells.
• Paracrine: targets cells that are in the vicinity of original cells that transmits the signals. Example- neurotransmitters.
• Endocrine: signal is transmitted via bloodstream through hormones produced by cells.

Importance of cell signalling– Cell signalling basically allows cells to respond and perceive to external environment allowing their growth, development, immunity. Without cell signalling it’s not possible to handle complex body mechanisms and perform important biological functions. Errors in cell signalling process results in diseases like cancer, diabetes.