Cellular function and signalling

What is cell signalling?

process of a cell responding to an external signal and altering its activity accordingly.

What is the receptor lock and key theory?

Specificity is compared to a lock and key

Receptor on cell picks up signal and then cell undergoes changes etc

There is a **high specificity** related to the ligand (signal) and the receptor. E.g:

different ligand can trigger different responses.

receptors can only bind to a certain ligand.

What are the types of communication?

* **Contact-dependent (Juxtacrine)**: signalling cell and target cell are in contact
* **Paracrine**: signalling cell and target cell are in proximity
* **Autocrine**: the cell produce the signal and respond to it
* **Endocrine**: signalling cell and target cell are distant (signal arrives through the bloodstream)
* Synaptic: depends on neurotransmitter

What is juxtacrine signalling?

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Cells need to be in contact 

e.g cardiac muscle cells which are in close contact (have gap junctions) and the message is sent from one cell to the other through these gap junctions. 

WHat is paracrine signalling?

Signals travel relatively short distance but the cells are not in contact.

E.g inflammation- cells in connective tissue sending message to epithelial cells to heal

What is autocrine?

Message comes form inside the cell

target and signalling cell are the same

What is endocrine?

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* Signals produced by specialised cells that will be released into the bloodstream where it will travel and find receptor in target cells in target organs
* Called hormones

What is synaptic signalling?

electric signal triggers release of specific chemical ligands in signalling cells (neurotransmitter).

travels over the synapse and causes a chemical change in the target cell- usually a muscle or nerve cell.

What are the 4 stages in signalling?

1\.    Signalling (send message)



2\.    Reception (receive message)



3\.    Transduction- The moment the cell interprets the message. (understand message)



4\.    Response (act upon it)

WHat are the types of signalling molecules?

* **Growth factors**
* **Hormones**
* **Vitamins**
* **Chemicals**
* **Enzymes**
* Sugars

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Types of responses by cells

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* Growth (cell division)
* Differentiation
* Migration
* Metabolism
* Cell survival
* Apoptosis
* Gene transcription
* Secretion
* Contract / relax

Example of when the same signal can be present in physiological and pathological conditions

This proves the point - same signal and different receptor = different response

* VEGF (growth factor)

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* Macrophages produce and secrete VEGF during wound healing to induce angiogenesis (new blood vessels)

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* Cancer cells produce and secrete VEGF to stimulate greater blood supply (allowing the tumour to grow more)

What are the types of receptors?

1. **Intracellular receptors**
2. **Membrane receptors: Ion channel-linked, G protein-linked (7-TM), Enzyme-linked**

What are intracellular receptors?

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* AKA internal receptors or cytoplasmic receptor
* Signal has to be hydrophobic – so it can pass through cell membrane
* Signal is then transported into the nucleus to induce transduction
* (e.g. influences cell transcription)
* Examples: steroids, nitric acid

What are membrane receptors?

* Cell surface, membrane-anchored, or integral proteins that bind to external ligand molecules
* Transports signal to inside of cell or converts an extracellular signal into an intracellular signal
* Ligands that interact with cell-surface receptors do not have to enter the cell

What are the 3 components of membrane receptors?

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* External ligand-binding domain (in extracellular domain)
* Hydrophobic membrane-spanning region
* Intracellular domain

What are the types of membrane receptors?

Ion channel linked receptors

G protein linked receptors

Enzyme linked receptors

What are ion channel linked receptors?

* When the signalling molecule binds to the receptor, the gate opens which gives passage to other signalling molecules.
* Very rapid process - binding of few ligands enables many of them to enter cell

(not to be confused with voltage gated sodium ion channels which aren’t activated by a specific ligand)

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What are G protein linked receptors?

It is the middle man

This receptor is a combination of three proteins together: the receptor, G protein and target enzyme/protein.

The ligand binds to the receptor and the G protein changes its confirmation so that it can bind to the target protein and alter its activity.

What are enzyme linked receptors?

single transmembrane protein that has its ligand binding site outside the cell and their enzyme-binding site inside.

presence of the ligand triggers a catalytic response on the intracellular component of the enzyme

What are receptor tyrosine kinases?

are a type of enzyme linked receptor

are the cell surface receptors for: Growth Factors, Cytokines and Hormones.

on binding with ligand it causes phosphorylation of internal enzyme component

phosphate added to tyrosine group

outcome of this activation causes downstream effects and activation of other proteins

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Dysregulation or hyperactivation of this cascade can have a critical role in the development and progression of cancers.

Therapeutic target and signalling pathways

Can manipulate the cascades from Receptor Tyrosine Kinase receptors to be used as a therapeutic agent.



If we block the ligand from binding to its specific receptors, we can stop the outcome of a particular ligand.

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e.g, since cancer cells produce VEGF to stimulate greater blood flow to the tumour (in order to provide it with nutrients) if we block the VEGF binding site, we can prevent the cascade and stop tumour growth- by cutting off nutrient supply.



We could either use inhibitors or monoclonal antibodies as the blocking site hence the ligand can no longer bind.



Or we could use a drug which directly inhibits the activity of the enzymes in the cascade.

Personalised Therapy

Drugs which are specific to the specific receptor/hormone that a patient’s cancer is addicted to. We can then tailor specific drugs which inhibit that specific pathway and prevents tumorous growth.