Lecture 1 - Cell communication (introduction) Flashcards
What are the 3 parts for the conceptual basis for communication?
- communication for development
- communication for homeostasis
- communication breakdown in old age
What are the 3 characteristics of communication?
- speed
- duration
- mechanism
What are the 4 different types of signals?
- contact-dependent
- synaptic
- paracrine
- endocrine
What is an example of contact dependent signalling in Drosophila?
Notch pathway signalling that spaces R8 photoreceptors in the drosophila eye disc morphogenetic furrow (development of eye)
What is an example of synaptic signalling?
Neurons - they may a very small number of targets
What is an example of paracrine signalling?
Hedgehog (Hh) expression = Decapentaplegic (Dpp) ligand expression - secreted by cells in the middle of Drosophila wing disc.
This activates downstream transcription factor Mad (red).
Why do Hedgehog and Decapentaplegic require paracrine signaling?
As they are large proteins, therefore require paracrine signaling to cause the downstream effects necessary.
What is an example of endocrine signaling?
Adrenaline (produced by adrenal glands) acts on adrenergic receptors to produce a range of physiological responses.
What is an example of endocrine signaling in bees?
Queen produces pheromones that control hives of tens of thousands of workers
What are 3 ways cells can respond to signaling?
- altered metabolism
- altered gene expression
- altered cell shape or movement
Give an example of how metabolic enzymes can lead to altered metabolism? (think yeast metabolism)
There can be changes in yeast metabolism triggered by different sugars provided as energy source
Describe how gene expression might be altered
Through gene regulatory proteins - expression of Iroquois family genes in the E12 mouse embryo
Describe how cell shape or movement can be altered
Human neutrophil chasing signal given off by Saphylococcus aureus
Describe how a paracrine signalling works
Extracellular signal molecule –> receptor protein –> intracellular signaling –> effector proteins
What is a morphogen gradient?
a special case where the response of cell to a signal occur at specific thresholds
Describe how a morphogenic gradient defines the anterior parts of the resulting embryo in Drosophila
Bicoid (Bcd) mRNA is deposited in the anterior and forms a gradient.
- gene expression downstream of Bcd has sharp boundaries
- thresholds of signal trigger sharp on/off gene expression
What 3 ways can cells respond to signalling?
- changing structure of existing protein (e.g. ion channels - very fast)
- changing the post translational modification (e.g. phosphorylation (quite fast)
- changing protein levels via gene expression (slow)
Describe the formation of myeloproliferative neoplasms and what they are associated with`
A mutation in the negative regulatory domain of JAK2, which leads to overproduction of erythrocytes. Associated with >95% of blood cancer patients.
Describe the formation of chronic myeloid leukaemia
Bcr-Abl fusion protein that causes sustained Abl tyrosine kinase expression by the Bcr promoter/enhancer region leading to CML
What are 2 examples of how a lack of regulation of tyrosine kinase leads to disease?
- Myeloproliferative neoplasms
- Chronic Myeloid Leukaemia
At what stages may a signalling pathway be regulated?
- Extracellular/ligand/receptor
- Intracellular/transduction of signal
- Effectors can ‘feedback onto their own pathway
Give an example of how an effector might produce a positive feedback
Notch pathway lateral inhibition (produces a binary outcome)
Give an example of how an effector may create a negative feedback
JAK/STAT pathway down regulation by SOCS negative regulator
Why is it useful to alter the activity of a protein?
switching a protein on/off is more efficient than creating and destroying them.
What are 2 ways to alter protein activity?
- signaling by phosphorylation (addition of phosphate group)
- signaling by GTP binding
How are GTPase activity levels regulated?
Through modulating GAP (GTPase-Activating Protein) and GEF (Guanine Nucleotide Exchange Factor) levels
What do GAPs do?
GTPase activating proteins - GTP to GDP through hydrolysis
- INactivating them
What do GEFs?
Guanine Nucleotide Exchange Factor - GDP to GTP
- activating GTPases
When are small GTPases active/inactive?
GTP bound - active
GDP bound - inactive
What can occur when GTPases are active?
They can interact with their effector proteins and trigger specific cellular functions
What are the 2 major groups of protein kinases?
- serine / threonine kinase
- tyrosine kinase
What do protein kinases do?
Add phosphates
Describe the role of Serine/Threonine kinase
- Serine <–> Phospho-serine
- Threonine <–> Phospho-threonine
Describe the role of Tyrosine kinase
Tyrosine <–> phospho-tyrosine
