Cell communication Flashcards
Why do cells communicate
Need to be able to respond to a cell, and as part of a whole tissue
Respond to signals from other cells and from the environment
What are the two subtypes of cell signalling?
Local or long distance
What is local signalling
Signals act on nearby cells
Growth factors such as fibroblast growth factor
Neurotransmitters such as acetylcholine - ACh
What is panacrine signalling
Cells release signals that act on nearby cells, producing local effects
What is synaptic signalling
Hormones released from endocrine cells travel via the cardiovascular system to act on specific distant cells
What are the two subtypes of local signalling
Panacrine and synaptic
What is long distance signalling
Signals act from a distance
Hormones produced by specialised cells travel via circulatory system to act on specific cells
e.g insulin from pancreas bind to insulin receptors initiating a cascade resulting in glucose uptake
What are the three main steps of cell signalling
Reception
Transduction
Response
What happens in reception of cell signalling
Signalling protein (primary messenger) binds to a receptor protein. Results in shape and/or chemical change in the receptor protein
What happens in transduction of cell signalling
Altered receptor activates another protein. The activated protein (often enzyme) may cause a relay of changes.
Relay molecules (second messengers) e.g cAMP and IP3.
Multiple other proteins may be activated
What happens to each activated protein in transduction
Each activated protein causes a series of changes, this is often via phosphorylation, known as a phosphorylation cascade
What happens in response in cell signalling
All of the activated proteins cause one or more functions to occur in the cell. This is where the cell actually does something
How are receptors specific
The human body simultaneously sends out different chemicals and molecules which are all aimed at eliciting specific responses BUT only the target receptor on the target cell will interact with that signal and use it to activate signal transduction pathways.
Where does the specificity of receptors come from
3D molecule shape of the proteins involved
How is the cell receptor specifically created
Created through 3D shape of the receptor (lock and key
How is exquisite control of receptors possible?
Only certain cells at certain times will have particular receptors, meaning that while the signal may be widespread the transmission of the signal occurs only where it is needed
What are the two main types of receptors
Intracellular and Membrane bound/cell surface receptors
What are intracellular receptors
A primary messenger that is generally hydrophobic and/or small - lipid soluble, can enter the cell.
What kind of signalling uses intracellular receptors?
Sex hormone signalling such as testosterone, progesterone, oestrogen.
What are membrane-bound/cell surface receptors?
Primary messengers that is generally hydrophilic and/or large
Are membrane bound receptors polar or non polar
polar
Which is the most common method of cell signalling?
Membrane-bound/cell-surface receptors
What are the two types of membrane bound receptors
GPCR’s, receptor tyrosine kinase, and ligand gated ion channels
G proteins are molecular switches, what does this mean?
The molecular switches of the G protein are either on and off depending on whether GDP (inactive) or GTP (active) is bound
How many times do G protein receptors (GPCRs) span the plasma membrane
7 times
How many different GPCR’s are there and what are their function(s)
Hundreds of different GPCRs exist each with different ligands with diverse functions e.g development, sensory reception
What is the first step of the GPCRs process
1) At rest, receptor is unbound and G Protein is bound to GDP. The enzyme is in an inactive state.
What is the second step of the process of GPCRs
2) Ligand binds receptor, and binds the G protein. GTP displaces GDP. The enzyme is still inactive
What is the third step of the process of GPCRs
Activated G protein dissociates from receptor. Enzyme is activated to elicit a cellular response
What is the fourth step of the process of GPCRs
G protein has GTPase activity, promoting its release from enzyme, reverting back to resting state.
What are ligand gated ion channels/receptors?
Channel receptors that contain a ‘gate’.
Binding of ligand at specific site on receptor elicits a change in shape.
The channel opens/closes as the receptor changes shape
Ions can pass through channel
What is a ligand
A signalling molecule that binds specifically to another protein
What is an ion channel receptor
Membrane protein through which specific ions can travel, in response to ligand binding (aka ionotropic receptors)
What are steps in ligand gated ion channels
At rest, ligand is unbound and gate is closed.
Upon ligand binding, gate opens, specific ions can flow into cell.
Following ligand dissociation, gate closes back to resting
How does ion gated channels work
Channel receptors contain a gate where the binding of a ligand elicits a conformational change so the channel opens and allows ions to pass through. When the ligand unbinds the shape of the receptor changes again and the channel closes
What flows through ligand ion channels, and when?
Once a ligand binds to the receptor and causes a conformational change, ions such as Ca2+, Na+, K+ and Cl- can flow through
Which body system relies heavily on ligand gated ion channels, and why
The nervous system
Released neurotransmitters bind as ligands to ion channels on target cells to propagate action potentials
What are signal transduction pathways
Signals relayed from receptors to target molecules via a ‘cascade’ of molecular interactions
What is a typical phosphorylation cascade
Enzymes that transfer a phosphate group from ATP to another (specific) protein. Typically, this activates the protein.
Series of protein kinases each adding a phosphate to the next kinase
How is a phosphorylation cascade formed
Series of protein kinases each transfer a phosphate group from ATP to an inactive enzyme to activate it
What are phosphatase in regards to the phosphorylation cascade
Phosphatase are enzymes that dephosphorylate (remove phosphate) rendering the protein inactive, but recyclable
What are the typical residues (side chains) of proteins that are phosphorylated? what could this lead to
Serine or threonine residues
This means that mutations affecting these residues could be detrimental
What are primary messengers
The original signal molecule (ligand) that binds to a receptor, useful in signal receptor
What are second messengers
Intracellular molecules useful in signal transduction. They link the activated enzyme with the signalling cascade
What are second messengers (cAMP)
Another small molecule that is included in the cascade that activates further pathways
What does cAMP (second messengers) do and how is it made
When the G protein dissociates from the receptor and binds to an enzyme, it binds to adenylyl cyclase which catalyses the conversion of ATP to cAMP. cAMP acts as a second messenger by activating protein kinase A, which initiates a phosphorylation cascade
What are the most common second messengers
cAMP, calcium and IP3
Why is is calcium (second messengers) kept at low concentrations in the cell
To prevent cell damage - high Ca2+ can damage cells
How is calcium kept at low concentrations in the cell?
Using calcium pumps to pump calcium out of the cell or into the mitochondria or ER
What happens in CA2+ and IP3 in GPCR signalling
The activated protein phospholipase C hich then cleaves PIP2 (a phospholipid) into DAG and IP3
IP3 diffuses through cytosol and binds to gated channel in ER
Calcium ions flow out of ER down concentration gradient and activate other proteins toward a cellular response
What is PIP2
A phospholipid embedded in the plasma membrane
Why are there so many steps in signalling
Amplifies the response
Provides multiple control points
Allows for specifity of response and coordination with other signalling pathways
Examples of a cellular response that includes activation or regulation of ___
- Gene expression
- Alteratation of protein function to gain or lose an activity
- opening or closing of an ion channe;
- alteration of cellular metabolism
- regulation of cellular organelles or organisation
- rearrangement/movement of cytoskeleton
- a combo of any of these
Elaborate on how signals are for a limited time
Because activation usually promotes the start of deactivation, so that signalling is of short period of time.
Why is it important for signals to be for a short amount of time
To ensure homeostatic equilibrium so response is not execessive
What is cAMP broken down by and what does this mean
By the enzyme phosphodiesterase (PDE), so will no longer continue to activate protein kinase
Why is deactivation an important regulatory step?
Otherwise cascades can run rampant and cause problems or inappropriate activation of proteins
Is deactivation automatic
Yes
What is adrenaline stimulation of glycogen breakdown?
- Adrenaline acts through a GPCR, activates cAMP and two protein kinases in a phosphorylation cascade
- results in active glucogen phosphorylase which can convert glycogen to glucose 1-phosphate
What does amplification in adrenaline stimulation result in
Means that 1 adrenaline molecule can result in 10^8 glucose 1-phosphat molecule
What does glycogen breakdown result in, and what does this convert to
glucose 1-phosphate, which converts to glucose 6-phosphate which can then be used in glycolysis to generate ATP
What is glycogen
A long term energy store in liver and skeletal muscle
How does SARS-CoV-2 invade our respiratory tract?
ACE2 is the cellular receptor for the coronavirus
ACE2 in our respiratory tract is the lock and S protein on the virus is the key
