Module 9: Cell Signalling Flashcards
What is cell signalling?
- Transferring information from the outside of the cell to obtain a response inside the cell
- cells communicate by sending and receiving chemical signals
- this communication can take place over short or long distances
What are the 4 elements for cell communication? Is it for prokaryotes or eukaryotes
both eukaryotes and prokaryotes use the 4 following elements:
1. Signalling Cell
2. Signalling molecule
3. Receptor molecule (Receptor Protein)
4. Receptor cell (Responding cell)
Signalling in Bacteria
- Bacteria have been observed to take up DNA from the environment so its important to consider population of bacteria
- a small peptide was discovered to be continuously synthesized by pneumococcal bacterial cells
- cells express a receptor for this peptide on the surface
- when the peptide binds to the receptor the bacterium expresses genes that enable it to take up DNA from the environment
- if there a low density of bacteria, there’s low peptide levels
- signal falls below its critical threshold and gene expression is turned off
- if there’s a high density of bacteria then high peptide levels
- peptide is bound the signal is relayed by signal transduction to the nucleoid region
- genes are turned off on that produce proteins involved in DNA uptake from the environment
Four steps involved in signalling between cells:
- Receptor activation - binding of signalling molecule
- Signal transduction - transmission of signal into the cell
- Cellular Response - specific for the target cell
- Signal termination - stop response
Some receptors are cell surface protein that recognize what specific molecule?
ligands
- can be an extracellular ligand, molecules secreted by cells
- can be due to cell-to-cell contact or contact with extracellular matrix
Intracellular Receptor
some receptors are found inside the cell
- small, nonpolar signaling molecule
- ligand has to travel into the cell to bind to the receptor
When is the receptor activated?
once the signalling molecule is bound to the receptor on the responding cell, then it is considered turned on
The ligand interaction with the ligand-binding site is very similar to what?
the substrate/active site binding in enzymes
When a ligand binds to the ligand binding site on its receptor what happens?
a conformational change in the receptor triggers chemical reactions within the cytosol
Signal Transduction
- Once activated, the receptor transmits a message to the cell through the cytoplasm
- this transmits the reception of ligand binding to the receptor, the stimulus
- message can remain in the cytosol or go to the nucleus
- a series of distinct proteins that are activated/ inactivated in a particular sequence are often amplified.
What happens once the cell responds to the signal?
- response could activate enzymes, turn on genes, signal other cells, and cause the cell to divide or change shape
- the response will depend on the cell type, depends on specific proteins and signalling pathways in that cell
How is cell signalling terminated?
Once the signal has been received and acted upon, it is terminated and stops the cellular response
In multicellular organisms communication happens between what?
between cells within the same organism
- the distance between communicating cells varies
Cell communication is classified by what?
distance between the signalling cell and the target cell
- can be divided into long distance and short distance communication
Endocrine Signalling
- Long distance communication where the signalling molecules travel through the bloodstream
- Uses chemical signalling molecules, hormones
- produced by endocrine cells
- the target cell expresses the appropriate receptor for the hormone
Paracrine Signalling
- neighbouring cells communicate where the signalling molecule travels a short distance
- signalling molecule moves via diffusion, typically small & water soluble
- travel within a range of ~20 cells
Autocrine Signalling
- communicates with itself
- when the cell that secretes the signalling molecule is also the target cell
- used for defense if needs to react to environment
- leaves and comes back in, sends itself a signal
Paracrine and Autocrine signalling are especially important to multicellular organisms during what?
embryonic development
Contact-Dependent Signalling
- some signalling occurs because of direct contact between neighbouring cells
- does not work if there’s cells in between
- a transmembrane protein on the surface of one cell acts as the signalling molecule, a transmembrane protein on an adjacent cell acts as the receptor
- also called juxtacrine signalling
Intracellular Receptors
- nonpolar signalling molecules can pass through the hydrophobic core of the cell membrane
- these signals do not need a receptor on the outside of the cell
- instead, one inside the cell, the ligand can bind to receptor proteins located in the cytosol or in the nucleus which activates the receptor
Cell Surface Receptors
- signalling molecules that are polar cannot cross the cell membrane
- bind to transmembrane proteins that are cell-surface receptors
- binding of ligand to the cell-surface receptor causes a change in conformation which activates the receptor
What are the three main groups of proteins that take part in cell signalling?
- G protein-coupled receptors (GPCR’s)
- Receptor Kinase
- Ion channels
Where are GPCRs found?
found in virtually every eukaryotic organism
G protein-coupled receptors associate with what?
G proteins, they bind to GTP and GDP in the cytoplasm
What are the three subunits of G proteins?
- Alpha
- part of the G protein that binds to either GDP or GTP - Beta
- Gamma
What does it mean when the alpha subunit is bound to GDP?
that the three subunits are joined
Binding of the G protein to ATP or ADP regulates what?
G protein activity
When is a G protein active vs inactive?
active: when the G protein is bound to GTP
inactive: when it is bound to GDP
GPCR Activation
Activation happens when a ligand binds to the GPCR (it is inactive before then)
- once binded it activates the G protein by replacing GDP with GTP
- if bound to GTP, then the G protein is on and the signal continues to be transmitted
- the alpha subunit disassociates from the other subunits and binds to the target protein to activate the protein
GPCR Activation Example
- heart rate can be influenced by signals that activate via a GPCR system
- through epinephrine released from the adrenal gland (epinephrin is also known as adrenaline)
- when epinephrine binds to a GPCR on heart muscle, the binding activates the G protein
– GDP on the alpha subunit is exchanged with GTP - GTP-bound alpha subunit of the activated G protein then binds to and activates an enzyme in the cell membrane called adenylyl cyclase
– this enzyme converts the nucleotide ATP into small signalling molecule cyclic AMP, (cAMP)
– cAMP is a second messenger
– cAMP binds to and activates another enzyme, protein Kinase A (PKA)
– activated PKA phosphorylates proteins in the heart, which increases the rate of contraction - as long as epinephrine is bound to the receptor the heart rate will remain high
Kinases are enzymes that…
phosphorylate target proteins
Signal Amplification
- the signals produced by activated GPCRs are amplified
- means that a small amount of ligand can produce a large response in the target cell
Example: epinephrine - the signal is amplified in 3 places
1. each epinephrine-bound receptor activates multiple G proteins
2. each adenylyl cyclase molecule produces large amounts of cAMP
3. each active protein kinase A activates multiple protein targets
Signal Termination
With example
- the time a ligand is bound to its receptor depends on how tightly the receptor holds on to it
– known as binding affinity
Example: epinephrine - epinephrine leaves the receptor, which reverts to its inactive conformation, no longer activates G proteins
- G proteins convert GTP to GDP, becoming inactive
- this inactive adenylyl cyclase, therefore no cAMP is formed
- enzymes in the cytosol degrade cAMP and stops the activation of more protein kinase A molecules
- phosphatases remove phosphate groups from activated proteins, this inactivates the proteins
Receptor Kinase
- a receptor kinase becomes active when a ligand binds
- the receptors associate into dimers, dimerization
- this results in the phosphorylation of another protein that transmits the signal from outside the cell to inside the cell
Receptor Kinase Examples
- receptor kinase signalling is used in multiple processes
Examples: - the formation and elongation of structures called limb buds that become our arms and legs
- insulin signalling, allowing us to transport glucose across the plasma membrane into the cytosol
- wound healing, like after a paper cut
How a paper cut heals
- if there is a small paper cut the need to be repaired
- when blood encounters the damaged area the platelets in the blood release proteins including platelet-derived growth factor - PDGF
- repair is stimulated by PDGF, it binds to PDGF receptor kinases on the surface of the cell
– the receptors dimerize and become active - the phosphorylated receptors help activate other proteins in the cell
– in the MAP kinase pathway, the cytoplasmic signalling protein activated is Ras
– GTP-bound Rad triggers a kinase cascade
– at the end of the cascade the activated kinase enters the nucleus
— turns on expression of genes associated with cell division
– the pathway is terminated when the GTP is replaced by GDP on Ras
Ion Channels
- ion channels can change the flow of ions across the cell membrane, either into (influx) or out of (efflux) the cell
- ion channels can be gated
- the gate regulates the movement of ions across the channel
What are the three types of gated channels?
- Ligand-gated : responds to binding of a signalling molecule
- Voltage-gated: responds to changes of voltage in the cell
- Mechanically-gated: respond to force applied to cell
What happens when the gate for gated ion channels is open vs closed?
- if gate is closed it prevents the movement of the ion
- if gate is open it allows the movement of the ion
