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Cellular Signalling Notes

Pharmacology Notes > BIOL21141 Cell Membrane Structure & Function Notes

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Topic 2 - Cellular Signalling

Extracellular Stimuli

Transmembrane signalling is the information transfer across the plasma membrane to produce an appropriate response inside the cell.

Stimuli can be classed into 2 groups: Light (Proteins convert into chemical and electrical form) or Chemical
(Hormones, Neurotransmitters, etc).
Extracellular stimuli act via receptors, specialised proteins for the detection of an external stimulus. Unicellular organisms need this for information on their surrounding environment, whilst multicellular organisms need them to co-ordinate the functions of cells.

Types of Intracellular Communication
Long Range:

 Synaptic Signalling
 Endocrine Signalling
Short Range:

Paracrine Signalling - A diffusible signal from an adjacent cell to produce a response.
Autocine Signalling - A signal arising from and binding to the same cell (Can induce [+] or [-] Feedback).
Juxtracrine (Contact-dependent) Signalling - Signals arising from the contact to an adjacent cell.

The Components of the Signalling Pathway

Extracellular Stimulus - There are 100s of these in higher eukaryotes, they ae mostly chemical, may act at very low concentrations and are usually reversible and graded.

Receptor Protein - This has a very high affinity for the ligand, and its binding activates a cascade of intracellular events. These are usually on the cell membrane, which acts as the communication protein. These
Cell Surface Receptors include: Ligand-Gated Ion Channels, GPCRs and PDGF Receptors (Tyrosine

Signalling Machinery - This undergoes multiple molecular changes in order to relay and amplify information.

Effectors - This produces the response. Signalling pathways can often act via the same stimulus, receptor,
intermediates, but with different effectors producing different responses.

'Off' Switch - This is the mechanism for restoring the basal activity, once stimulation has ceased.

Signalling Pathways

The activation of a receptor may activate more than one pathway through Bifurcation, and these pathways may interact through Crosstalk.
Signalling pathways often use Enzyme Activation as a means of producing Amplification, they also often use:
Protein Phosphorylation and Second Messengers.

Protein Phosphorylation 

Protein Phosphorylation is a post-translational modification which involves the covalent addition of a phosphate group. Phosphorylation occurs of Serine, Threonine and Tyrosine and around 50% of all proteins are modified by phosphorylation, by very specific Protein Kinases.

Second Messengers

Second messengers are small, intracellular non-protein signalling molecules. They are typically low in unstimulated cells and then their amount rapidly increases once stimulated to allow amplification.
They must diffuse rapidly, as well as be broken down rapidly.
They interact with specific binding proteins through allosteric activation and often produce phosphorylation.

G Proteins

G Proteins act as molecular switches and exist in GTP = active, and GDP = inactive forms.
There are 2 subclasses of G proteins: Heterotrimeric and Small/Monomeric.

Heterotrimeric G proteins - Heterotrimeric G proteins have 3 subunits: α, β, γ. These are linked to a GPCR
in a signal relay.
Monomeric G proteins - Monomeric G proteins are activated by Guanine nucleotide exchange factors, and these controls many processes, such as membrane trafficking and nuclear transport.

Signal Amplification

Signal amplification is required to ensure a robust, effective response from even a small initial stimulus.
As a result, signalling pathways contain several amplification steps, to ensure the signal does not 'run down'.
This usually occurs through the activation of enzymes, or ion channels.

Signal Termination

Signal Termination responses are usually transient, and only occur when appropriate, and once removed the system resets. These termination mechanisms (eg: enzymes that destroy second messengers) occur at multiple points of the signalling pathway, acting as checkpoints, and are usually always active in unstimulated cells.

Ligand Gated Ion Channels

In ligand gating, a ligand such as a neurotransmitter binds to a receptor causing a conformational change,
leading to the activation of a signalling pathway.

The charge of some ligands prevents them from crossing the membrane, so specialised membrane transporters bind to them, open and allow selective movement across the membrane, allowing electrochemical gradients to exist across membranes.

Enzyme Coupled Receptors

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