Cellular communication Flashcards
List the mechanisms of cell communication and signalling
There are several mechanisms of cell communication and cell signalling:
- autocrine: the cell expresses the receptor and secretes the ligand, i.e. ‘talking to yourself’
- juxtacrine: one cell has the ligand, kept on the surface, the other cell has the receptor, the two cells come into direct contact, ‘talking to your neighbour’
- paracrine: ligand is secreted by one cell but it does not enter circulation, and the targeted cell is reached by diffusion through the interstitial fluid, ‘talking to your group’
- endocrine: ligand is secreted by one cell and reaches the target cell via circulation, ‘broadcasting to the entire world’
Describe the role of gap junctions in cell communicaiton
Role of gap junctions in cell communication i.e. juxtacrine signalling
Intercellular channels are specialised and allow direct communication and exchange of small molecules (ions and metabolites) between adjacent cells.
The most common protein involved
are connexins and allow coordinated cellular responses, and synchronisation of cellular activities. This is important in embryological development (sending signals to instruct cell how to behave), muscle contraction and neurological response.
This mode of transport is very efficient for small molecules, especially for hydrophilic molecules. Examples include Ca2+, glutamate, secondary messengers and signalling molecules: ATP, IP3, cAMP, cGAMP, polyamines and glutathione.
Also useful in other systems e.g. in endothelial cells
Describe the general features of a signalling cascade
Features of signalling cascade
The initiation of the signalling cascade is dependent on receptor ligand interactions.
An example is a transmembrane protein receptor, a site that can recognise another molecule e.g. another protein, acts as a ligand.
Upon binding, the signalling cascade is initiated (a chain of events), which ultimately results in a specific biological response e.g. increased gene expression, cell division and apoptosis.
The series of reactions in the cytoplasm is triggered by ligand binding. Signalling cascades are important for many physiological processes such as immune responses, hormone regulation and neuronal signalling.
Signal transduction: EC signals are detected and converted into intracellular responses through a signalling cascade.
The anatomy of a signalling cascade:
1. Reception: the binding of an EC single molecule to a specific receptor; ligand is the primary messenger; as a a consequence, the receptor change s shape
2. Transduction: activation of a second messenger molecule followed by a series of IC signalling events; signal is usually amplified during transduction
3. Response: gene expression, opening or closing ion channel, enzyme activity etc.
Note: the amplification as signal is transduced: This enables a response to small changes e.g. in changes of concentration of ligand, a single photon of light in case of eye/retinal cells
List the events underlying cell signalling by GPCRs
GPCRs are G-protein coupled receptors
They are transmembrane receptors
1. ligand bind to receptor e.g. adrenaline to an adrenergic receptor
2. G proteins which is bound to IC surface, releases one of its subunits with teh release of GDP and binding to GTP
3. subunits activates an enzyme e.g. AC, which inteurn activates a secondary messenger cAMP
4.cAMP activates other cellular enzymes, eg PKA - which generates effector molecules e.g. active transcription factors
5.this then initiates sthe cells reposne to inital stimulus e.g. translocation of transcription factoors to nucleus, initiating transcription
notes about signalling by GPCRs:
- ligand binding induces a conformational change
- GPCR signalling is controlled by cAMP degradation, which reverses the action of PKA
signal is amplifeid 100 mil times on amplificaiton i.e. An increase in ligand leads to a very large increase at the cellular, and the reverse is true (a decrease in ligand leads to a very large decrease at the cellular end)
List other examlpes of receptors and secondary messengers
Tyrosine kinase receptor pathway
- RTKs are anchored to the membrane and have access to the environment
- ligand interaction that leads to receptor dimerisation
- this leads to autophosphorylation of Tyrosine residues on the receptor creates docking sites for the secondary messengers
- this in turn activates effector proteins and cellular response
- examples of the cellular response include proliferation, growth, differention, adhesion, migartion, survival
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The same receptor, but different ligands
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The FasL apoptosis pathway is initiated by the binding of FasL to its receptor, Fas, on the cell surface.
This results in the aggregation of multiple Fas receptors forming the DISC. The DISC recruits and activates caspase-8 which in turn activates downstream effector caspases, such as caspase-3, leading to cell death.
TNFa binding to the same receptor leading to an elevated secretion of inflammatory mediators, as opposed to apoptosis i.e. triggers a different chemical cascade via a different secondary messenger.
Note: light can also be a ligand, it is not always small molecules.
Define synapse
Synapses
Synaptic communication is a mode of communication employed by neurons. It occurs in a specific location and does not leave.
- the action potential (electrical impulse) presynaptic terminal and triggers the opening of voltage-gated calcium channel, allowing calcium ions to enter the terminal
- calcium ions causes snaptic vesicles containing neurotransmitters (NTs) to fuse with the presynaptic membrane and release their contents into the synaptic cleft
- NT diffuses across the synaptic cleft and bind to specific receptor molecules on the postsynaptic membrane
- Binding of NTs to their receptors causes conformational changes in the receptor molecules, leading to the opnening or closing of ion channels and subsequent changes in the membrane potential of the postsynaptic neuron
- Electrical impulse (action potential) is generated by the post-synaptic neuron…and so on
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- keeps information flow regulation (no dev)
- very quick in comparison with hormonal communication–> results in a response, and communication moves quickly from one end of the body to another
Describe steroid hormones
Steroid hormones circulate bound to a carrier protein. They detach from the carrier and pass into the cytoplasm freely because steroids are hydrophobic.
Steroid hormones do not require a signalling cascade. Instead steroids are trafficked to the nucleus where they regulated gene expression directly by binding to DNA.
regulates gene expression on TF behaviour
DEscribe EV dependent communicaiton
xtracellular vesicle dependent communciation:
Cell to cell communication does not always involve receptors. Often material is transferred from one cell to another causing the recipient cell to respond in a certain way.
EV communication is a form of paracrine action.
EV biogenesis is generated via budding of the plasma membrane or the endosomal membrane. EVs are classified beased on their size and biognesis pathways.
The types of EVs include:
- exosomes (which are derived from endosomes, budding from the Golgi)
- microvesicles and apoptotic bodies (plasma membrane derived)
The cargo transported by EVs includes proteins, lipids, RNA and DNA; it is actively selected by cells.
EV release is mediated by fusion with the cell membrane.
EV transport can occur locally i.e. by paracrine signalling or systemically via circulation (endocrine signalling).
EV uptake occurs via receptor mediated uptake or direct fusion with the cell membrane.
EV cargo controls gene expression, protein synthesis, signalling pathways, immune responses and metabolic activities.
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Describe tunnelling nanotubes
Tunnelling nanotubes are recently discovered structures.
Tunnelling nanotubes are thin, dynamic membrane channels that connect cells and enable intercellular communication.
Tunnelling nanotubes facilitate the transfer of cytosolic molecules, organelles, pathogens between neighbouring cells.
Tunnelling nanotubes are involved in immune surveillance, development, cancer metastasis and neurodegenerative disease.
The mechanism of formation remains poorly understood.
Describe links between cell signalling and drug discovery research
Understanding cell signalling is paramount to the discovery of new treatments.
Advanced biological systems employing gene expression profiling, simulation studies and direct biochemical methods to understand the outputs of cell signalling.
Most drugs target GPCR receptors or other elements of the signalling cascade (e.g. kinases).
Another major target is ion channels.
