L1 - Introduction to cell signalling Flashcards
What is cell signalling?
A complex system of communication that governs basic cellular activities & coordinates cell actions
Cell signalling affects a cells ability to…
Regulate cellular processes
Respond to its environment
Cell signalling affects…
- Development
- Tissue repair
- Immunity
- Movement
- Diseases
What does cell survival depend on?
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
Importance of cell signalling in humans
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
What happens when we get defects or dysregulation in signalling pathways?
Disease
What are the 5 basic types of cell signalling?
- Gap junctions
- Autocrine
- Paracrine
- Endocrine
- Synaptic
No distance signalling
Gap junctions
Short distance signalling
Autocrine
Paracrine
Long distance signalling
Endocrine
Synaptic
What are gap junctions?
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
Example of direct contact signalling
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
What is autocrine signalling?
Cell signals to itself
Example of autocrine signalling
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
What is paracrine signalling?
Cell signals to neighbouring cells
Examples of paracrine signalling
Wnt & Hedgehog signalling pathways
Inflammatory mediators
Paracrine signalling
Cancer cell migration control through a paracrine loop
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
Paracrine signalling
Histamine release by mast cells during allergic reaction
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
Paracrine signalling
Neuronal signalling
Electrical signal (fast communication) along the nerve cells trigger neurotransmitter release
Neurotransmitter is a chemical signal
What does a neurotransmitter do?
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
Endocrine cells
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
Synaptic signalling
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
Types of signals received by cells
Signalling molecules
1 signal can cause a multitude of cell responses in the target cell
Intracellular & extracellular signals
What are signalling molecules?
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
Intracellular & extracellular signals
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
How do cells convert an extracellular signal to a cellular response?
RECEPTION
TRANSDUCTION
CELL RESPONSE
What is reception?
The target cell detects a signalling molecule present in the exogenous environment
What is transduction?
Signal is converted into another signal & relayed by molecules
What is cell response?
Specific cellular effects produced in response to signalling molecules
Challenges associated with cell signalling
1 signal can have different effects in distinct cell types
Multicellular organisms are constantly exposed to a variety of extracellular signals
Solution to 1 signal having different effects in distinct cell types
Different cell types have different receptors for the same signal & induce different signalling cascades
• Muscarinic acetylcholine receptors
• Nicotinic acetylcholine receptors
Solution to multicellular organisms constantly being exposed to a variety of extracellular signals
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
Characteristics of cell signalling
SPECIFICITY
INTEGRATION & COORDINATION
AMPLIFICATION & FEEDBACK
Specificity in cell signalling
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
Integration & coordination in cell signalling
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
Feedback loops in cell signalling
At each step, feedback loops can modify the signal & the output acts back to regulate the process
What is deactivation?
Degradation / recycling of molecules
What is adaptation/desensitisation?
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
