L1 - Introduction to cell signalling

Question 1

What is cell signalling?

Answer 1

A complex system of communication that governs basic cellular activities & coordinates cell actions

Question 2

Cell signalling affects a cells ability to…

Answer 2

Regulate cellular processes

Respond to its environment

Question 3

Cell signalling affects…

Answer 3

• Development
• Tissue repair
• Immunity
• Movement
• Diseases

Question 4

What does cell survival depend on?

Answer 4

Depends on receiving & processing information from the environment

A cell is exposed to 100s of different extracellular signal molecules but must respond selectively to a limited set of signals

Question 5

Importance of cell signalling in humans

Answer 5

During embryological development, cells exchange signals to determine which specialised role each cell will adopt

Specialised cells: must communicate to form a tissue & maintain its function

Different cells (cell types) must produce a coordinated response to support the organism as a whole

Question 6

What happens when we get defects or dysregulation in signalling pathways?

Answer 6

Disease

Question 7

What are the 5 basic types of cell signalling?

Answer 7

• Gap junctions
• Autocrine
• Paracrine
• Endocrine
• Synaptic

Question 8

No distance signalling

Answer 8

Gap junctions

Question 9

Short distance signalling

Answer 9

Autocrine

Paracrine

Question 10

Long distance signalling

Answer 10

Endocrine

Synaptic

Question 11

What are gap junctions?

Answer 11

Cytoplasmic channels between adjacent cells: connect cytoplasm to adjacent cells

Maintain homeostasis in connected cells for ion balance

Can allow passage of signal molecules: electrical & metabolic coupling between cells

They provide metabolic cooperation between adjacent cells

Question 12

Example of direct contact signalling

Answer 12

The APC

Antigen display: becomes the message passed from macrophage to T helper cell

APC: APC presents the antigen complexed with MHC II on its surface to be recognised by the helper T cell

Leads to the activation of other immune cells

Question 13

What is autocrine signalling?

Answer 13

Cell signals to itself

Question 14

Example of autocrine signalling

Answer 14

IL-2 secreted by monocytes in response to external stimuli can bind to receptor on secreting monocytes

Secretion of growth/survival factors by tumour cells

Commonly used by immune cells

Question 15

What is paracrine signalling?

Answer 15

Cell signals to neighbouring cells

Question 16

Examples of paracrine signalling

Answer 16

Wnt & Hedgehog signalling pathways

Inflammatory mediators

Question 17

Paracrine signalling

Cancer cell migration control through a paracrine loop

Answer 17

Production of epidermal growth factor (EGF) by tumour-associated macrophages (TAM) to increase the invasiveness & migration of neighbouring breast tumour cells that express the EGF receptor (EGFR)

Secretion of colony-stimulating factor 1 (CSF1) by invasive tumour cell recognised by tumour-associated macrophages expressing CSF1R receptors

Results in the migration of cancer cells towards macrophages

Clever way of using the immune system to its advantage

Question 18

Paracrine signalling

Histamine release by mast cells during allergic reaction

Answer 18

When exposed to pollen, pollen binds to IgE on the mast cell

This activates the mast cell

Degranulation occurs causing the release of histamine

Histamine works on the local environment to increase vascular permeability causing runny nose & watery eyes

Sneezing as a result of histamine acting on neurones

Question 19

Paracrine signalling

Neuronal signalling

Answer 19

Electrical signal (fast communication) along the nerve cells trigger neurotransmitter release

Neurotransmitter is a chemical signal

Question 20

What does a neurotransmitter do?

Answer 20

Diffuses across synapse
Binds to receptor on other neurone
Triggers responses in cells or target tissues (neurons, muscles, or glands)
Remains in synapse – broken down after use

Specificity: determined by synaptic contact between secreting neuron & target cell

Can be inhibited to control the amount of signal travels – modulation

Question 21

Endocrine cells

Answer 21

Secrete hormones into the blood where hormones travel to specific target cells that recognise them

Specificity: target cells have receptors for binding a specific hormone

Question 22

Synaptic signalling

Answer 22

Neurones can have very long axons & target cells far away

Neurones secrete neurotransmitter

Specificity: arises from the synaptic contacts between a nerve cell & the specific target cells

Question 23

Types of signals received by cells

Answer 23

Signalling molecules

1 signal can cause a multitude of cell responses in the target cell

Intracellular & extracellular signals

Question 24

What are signalling molecules?

Answer 24

Mostly chemical signals

Act either locally, at short range or long distance

Act at very low concentrations (typically ~ 10-8 M) - signal amplification

Recognised with high affinity by specific receptors

Question 25

Intracellular & extracellular signals

Answer 25

Water soluble signal molecules bind EC domains of cell-surface receptors (cannot readily cross membrane) • Eg. peptide hormones, growth factors, hydrophilic neurotransmitters Small, hydrophobic signal molecules can pass through the plasma membrane & bind to intracellular receptors in the nucleus or cytoplasm • Eg. steroid hormones & NO

Question 26

How do cells convert an extracellular signal to a cellular response?

Answer 26

RECEPTION TRANSDUCTION CELL RESPONSE

Question 27

What is reception?

Answer 27

The target cell detects a signalling molecule present in the exogenous environment

Question 28

What is transduction?

Answer 28

Signal is converted into another signal & relayed by molecules

Question 29

What is cell response?

Answer 29

Specific cellular effects produced in response to signalling molecules

Question 30

Challenges associated with cell signalling

Answer 30

1 signal can have different effects in distinct cell types Multicellular organisms are constantly exposed to a variety of extracellular signals

Question 31

Solution to 1 signal having different effects in distinct cell types

Answer 31

Different cell types have different receptors for the same signal & induce different signalling cascades • Muscarinic acetylcholine receptors • Nicotinic acetylcholine receptors

Question 32

Solution to multicellular organisms constantly being exposed to a variety of extracellular signals

Answer 32

Cells have a variety of signalling mechanisms & collections of receptors Signalling pathways integrate information to provide a coordinated response by sharing molecules between different pathways – organised in protein networks Feedback mechanisms

Question 33

Characteristics of cell signalling

Answer 33

SPECIFICITY INTEGRATION & COORDINATION AMPLIFICATION & FEEDBACK

Question 34

Specificity in cell signalling

Answer 34

Signal molecules should be specific to only reach target cells – Receptor specificity for the ligand – Transmission signal across the plasma membrane – Specific receptors expressed in distinct cell types

Question 35

Integration & coordination in cell signalling

Answer 35

Each cell receives multiple EC signals + many signalling molecules are diffusing about in cells If 2 or more signals have opposite effects on a metabolic pathway, the outcome result should reflect the integration of these signals to ensure a coordinated response Signalling may interfere with core physiological processes The intracellular relay system for the different signals interact (using common relay molecules) so that the presence of 1 signal modifies the responses to another

Question 36

Feedback loops in cell signalling

Answer 36

At each step, feedback loops can modify the signal & the output acts back to regulate the process

Question 37

What is deactivation?

Answer 37

Degradation / recycling of molecules

Question 38

What is adaptation/desensitisation?

Answer 38

Cells can adjust their sensitivity to a signal under prolonged exposure to a stimulus to decrease a cell response to that level of stimulus – Inactivation of receptor by endocytosis, degradation or phosphorylation Desensitisation may lead to tolerance & can lead to the loss of medicinal effectiveness of some medicines that are over prescribed