Cell Signalling Flashcards
How does a signal cause a change in a cell?
Signal - receptor - (amplification) transduction - responses
What are the 5 types of signals that can be involved in signal transduction?
- Endocrine signals - released from a gland and travel through the bloodstream to act on a distant target organ e.g insulin
- Paracrine signals - released from cells to act on adjacent cells
- Autocrine signals - act on the same cell that they are released from -gh
- Cell-cell signalling - where the secretory cell is directly attached to the target cell by the signal e.g T cell activation.
- Ligand - the signals that bind to receptors
Describe the lock and key analogy for receptors:
This describes how each hormone has its own specific receptor. Only when the hormones or ligand engages with the correct receptor can it activate the receptor and trigger intracellular signalling leading to a response
How do drugs inhibit the receptor?
They can either partially block the receptor by not properly fitting into it or they can mimic its effect to inhibit intracellular signalling
Why does the receptor undergoes a conformational change when a hormone/ligand binds to it:
This is done so that signalling can occur without a hormone passing through the membrane allowing the receptor to act as a gate keeper or activity so that activity can be controlled at the cell surface
Describe the process of transduction:
The arrival of the signal then needs to be relayed through the cell - transduced. Cascades of molecular interactions relay signals from the receptors to target molecules in the cell. It usually involves multiple steps which can amplify a signal. It provides more opportuities for coordination and and regulation of cellular responses.
What are the 2 most common methods of signal transduction?
- Second messengers
2. Phosphorylation
Describe how second messengers work:
They are chemical signals that are not embedded in the membrane that can diffuse in and out of the cell to pass on the message. They change in concentration to convey info to the cell. And example of this is cAMP which can occur in many tissues and cells because other aspects are tissue specific
How does the same signal have different effects in different cells?
Because different types of cells have different collections of proteins which allow cells to detect and respond to different signals. Each cell has different proteins and pathways. Pathway branching and cross-talking further helps the cell to coordinate incoming signals
How does phosphorylation occur and what is it?
Phosphorylation and dephosphorylation act as a molecular switch that can turn protein activity up/down or on/off as required by the cell. Protein kinases transfer phosphates from ATP to protein. Many relay molecules in signal transduction pathways are protein kinases creating a cascade. Protein phosphotases do dephosphorylation
Describe signal amplification:
At each step the number of activated products is much greater than the preceding step. This means that only a very small amount of the initial hormone is required and a few receptors need to be activated to produce a response i.e each receptor may produce many second messenger molecules to amplify the signal
Describe the cellular response
The changes in chemicals result in the activation or inhibition of proteins e.g pumps enzymes etc
Describe the termination step of signal transduction:
After the cell has completed its response to a signal the process must be terminated so that the cell can respond to new signals. Signalling processes that fail to terminate can have highly undesirable consquences
Name and describe the 3 receptor classes:
- G protein coupled receptors GPCR’s - receptors that work with the help of a G protein
- Receptor tyrosine kinases RTK - receptors that attach phosphates to tyrosines to signal
- Ligand gated ion channel receptors - a signal molecule binds as a ligand to the receptor, opening the receptor gate and allowing specific ions to pass through a channel in the receptor into the cell
Describe the structural features of a GPCR:
7 transmembrane regions (serpintine) - with an extracellular N-terminus and intracellular C-terminus. There are 3 intracellular loops and 3 extracellular loops
Describe a simple GPCR signal transduction:
The binding of the hormone to its specific GPCR which spans the membrane results in a change in the structure of the protein and the activation of intracellular proteins (G-proteins). The G protein then interacts with adenylate cyclase which converts ATP into cAMP a second messenger molecule. This chemical activates protein kinase A (PKA) which is capable of phosphorylating many different proteins.
Describe the G proteins cycle:
The cycle starts with the inactive receptor and the inactive G protein in its GDP bound trimer state. The GPCR is activated by a hormone that causes a conformational change in the receptor that allows an interaction between the receptor and G protein to occur. The activated receptor then binds to the G protein via the a subunit. This interaction induces a conformational change in the a subunit which opens up the nucleotide binding site so that GDP can depart and GTP can take its place. At the same time, the a subunit dissociates from the by subunit. This dissociation allows transmission of the signal that the receptor has bound to a ligand. The a subunit interacts and activates a downstream effector protein. A single activated receptor can stimulate nucleotide exchange in many G proteins resulting in an amplified response. The effector then propagates the signal. The a subunit of the G protein has built in “intrinsic” GTP ase activity which hydrolyses deactivation of the a subunit. The bound GTP is like a clock that resets the alpha subunit after a certain period of time. The GDP form of a G protein can then reassociate with the by subunit to return back to the heterotrimeric protein.
Name and describe the 3 types of G proteins:
- Gs = stimulatory G protein that activates adenylate cyclase
- Gi = inhibitory G protein that inactivates adenylate cyclase
- Gq = activates a different receptor - phospholipate C
Describe how glucagon signalling occurs:
Glucagon is released from the islets of langerhans in the pancreas and they circulate in the blood to get to the liver where they bind to its specific receptor - the glucagon receptor. When blood sugar levels are low, these events are triggered ensuring energy availabilty
Describe epinephrine signalling:
It is released from the adrenal glands in the kidneys and circulates in the blood to go to the muscle tissues where it binds to its specific receptor - the epinephrine receptor. It is released during a fight or flight response.
What are 4 ways that the glycogen breakdown can be turned off?
- The hormones that stimulate glycogen breakdown are no longer present
- The inherent GTPase activity of the a subunit of the G protein inactivates G protein signalling
- Phosphodiesterase converts cAMP into AMP which does not stimulate protein kinase A
- A protein phosphatase removes phosphates from phosphorylase kinase and glycogen phosphorylase thereby inactiaving the enzymes
What is vision based on and describe the structure of the photoreceptors?
The absorption of photons (light) in the photoreceptor cells (rod and cones) in the eye. The photoreceptor molecules in rods is rhodopsin which is made of the protein opsin and a prothetic group 11-cis-retinal which is a light absorbing group (chromophore)
Describe the receptor signalling of rhodopsin:
When light is absorbed in the rods, it induces a specific isomerisation of the bound 11-cis-retinal to form all-trans-retinal (metarhodopsin). This form of rhodopsin activates the G protein transducin which interacts with the enzyme phosphodiesterase (by removing an inhibiting subunit) which converts cGMP to GMP. The reduction in cGMP concentration causes cGMP gated ion channels to close, leading to the hyperpolarization of the membrane and neuronal signalling to the brain
Describe the function of the cones in the eye:
These are for colour vision and they are mediated by 3 cone receptors which are homologues of rhodopsin. In humans there are 3 distinct photoreceptor proteins with absorption maximas at 426, 530 and 560 nm
