Cell Structure and Function - Cell Signalling Flashcards
What is local signalling?
Signals that act on nearby targets
What is paracrine signalling
Is when a cell produces a signal to induce change in nearby cells
What is an example of paracrine signalling?
Growth factors such as fibroblasts growth factor (FGF1)
What is synaptic signalling?
similar to paracrine signalling but have junctions (synapses) between the cell produces the signal ( neurotransmitters) and the cell receiving the signal
What is an example of synaptic signalling?
Acetylcholine
What is long distance signalling?
are signals that act from a distance. Hormones produced by specialised cells travel via circulatory system to act on specific cells (produced from endocrine system)
What are some examples of long distance signalling?
insulin from pancreatic beta cells bind to insulin receptors (tyrosine kinase type) initiating a cascade which results in glucose uptake
What are the two types of local signalling?
Paracrine and Synaptic
What are the two types of secreted signals?
Local and long distance
What is the first step of cell signalling?
Reception
What is reception?
Allows or causes the activation of a protein
What are the two types of receptors?
Intracellular and membrane bound/cell surface receptors
What are intracellular receptors?
Receptors inside our cells
They are the least common type of receptor
Where are intracellular receptors located?
Cytoplasm or cytosol of the cell
Examples of ligands that bind to intracellular receptors
Testosterone, estrogen, progesterone, thyroid hormones bind to receptors in the cytoplasm (they are hydrophobic so they can pass through plasma membrane) and move to nucleus as a complex
What is a ligand/primary messenger/signalling molecule?
a signalling molecule that binds to another (usually larger) specific protein
How can some ligands cross the plasma membrane to reach intracellular receptors? (In terms of their structure)
They are hydrophobic and/or small
What are membrane bound/cell surface receptors?
Receptors embedded in the plasma membrane of the cell/membrane of organelles
Function of membrane bound receptors?
To allow primary messengers that are hydrophilic and/or large to cross the plasma membrane
Examples of membrane bound receptors
G Protein Coupled Receptor, Receptor Tyrosine Kinase, ligand-gated ion channel
What are G-protein coupled receptors (GPCRs)?
A membrane bound receptor
Is also a transmembrane protein that crosses the plasma membrane 7 times
What are transmembrane domains?
The loops on a GPCR that are in the hydrophilic regions inside and outside a cell so they can interact with molecules
What are G proteins
the proteins that GPCR’s are coupled with. They are molecular switches that are either on or off depending on whether GDP or GTP is bound
What is GTP
An energy source, similar to ATP
What are the three steps of cell signalling?
Reception, transduction, response
What is the process of GPCRs?
At rest the receptor is unbound and the G protein is bound to GDP (inactive)
The enzyme is an inactive state
The ligand binds to the receptor and bind to the G-protein causing a conformational shape change of GPCR,
GTP displaces GDP causing the G protein to become activated. (The enzyme is still inactive)
The activated G protein dissociates from the receptor.
The enzyme becomes activated and has a conformational shape change.
It can now elicit a cellular response.
G protein has GTPase activity (release of GTP) which promotes its release from the enzyme and thus reverts it back to its resting state.
What are ligand gated ion channel/receptors?
A membrane bound receptor that contains a gate
It is close until a ligand (neurotransmitter) binds to it causing a conformational shape in the gate and thus opens
What is a receptor?
A molecule/protein which responds to a specific ligand
What is an ion channel?
Membrane protein through which specific ions can travel
What is an ion channel receptor?
Membrane protein through which specific ions can travel
Is in response to ligand binding
What is the process of ligand gated ion channels/receptors?
At rest the ligand is unbound and the gate is closed
When the ligand binds, the ligand gated ion channel is opened and specific ions can flow into the cell (down the concentration gradient)
Following ligand dissociation, the gate closes and goes back to the resting state.
What system relies heavily on ligand gated ion channels?
The nervous system.
Released neurotransmitters bind, as ligands, to ion channels on target cells to propagate action potentials
What is the second step of cell signalling?
Signal transduction
What is signal transduction?
Signals are relayed from receptors to target molecules within the cell via a ‘cascade’ of molecular interactions
What are protein kinases
Enzymes that transfer a phosphate group from ATP to another protein
Typically this activates the protein
What are phosphatases?
Enzymes that dephosphorylate (remove the phosphate), causing the protein to become inactive but recyclable
What does the last active protein kinases do?
Activates an inactive protein which then carries out a cellular response
What are the amino acids that are typically phosphorylated?
Serine or threonine
What is a secondary messenger?
A molecule that is generated when a specific substance attaches to a receptor on the outside of a cell membrane
This produces a change in cellular function
What is cAMP (cyclic AMP)?
A secondary messenger that is created when the activated enzyme adenylyl cyclase converts ATP to cAMP.
cAMP acts as a second messenger and activates a downstream protein (which could be the start of a phosphorylation cascade)
What disrupts the ATP to cAMP process
Cholera toxin
What is calcium?
A secondary messenger released from the ER
What is IP3?
Secondary messenger that diffuses through the cytoplasm and binds to a gated channel in the ER to release calcium ions
Where is there a low [Ca2+] ?
Inside the cell
Where is there a high [Ca2+]?
Outside the cell
Where is Ca2+ pumped to maintain low calcium levels inside the cell?
Extracellular space, ER, mitochondria
What is PIP2
Specific phospholipid in calcium signalling
What is Phospholipase C?
An enzyme that catalyses the splitting of PIP2 to IP3 and DAG
What is the process of IP3 and calcium acting as secondary messengers?
Here, the activated protein is phospholipase C which then cleaves PIP2 into DAG and IP3 diffuses through the cytosol and binds to a gated channel in the ER.
Calcium ions flow out of the ER down the concentration gradient and activate other protein towards a cellular response
An example of a cellular response of calcium?
Muscles use Ca2+ to contract
Why are there multiple steps on cell signalling between reception and cell response?
Amplifies the response
Provides multiple control points
Allows for specificity (temporal and spacial control)
Allows for co-ordination with other signalling pathways
What does the transduction of a signal lead to?
The regulation of one or more cellular activities like gene expression
Why is it important for cell signalling to be temporary/last a short period of time?
So that a cell can return to homeostatic equilibrium and be ready to respond again to another signal if required
What is phosphodiesterase?
An enzyme that converts cAMP to AMP
What blocks the action of phosphodiesterase?
Caffeine
What does viagra inhibit?
The specific cGMP which degrades phosphodiesterase
What is epinephrine?
Adrenalin
What is the function of active glycogen phosphorylase?
Converting glycogen to glucose
How many glucose 1-phosphate molecules result from 1 adrenalin molecule?
108
What is glycogen?
Long term store of glucose in the liver and skeletal muscle