Lecture 1 - Cell communication (introduction)

Question 1

What are the 3 parts for the conceptual basis for communication?

Answer 1

• communication for development
• communication for homeostasis
• communication breakdown in old age

Question 2

What are the 3 characteristics of communication?

Answer 2

• speed
• duration
• mechanism

Question 3

What are the 4 different types of signals?

Answer 3

• contact-dependent
• synaptic
• paracrine
• endocrine

Question 4

What is an example of contact dependent signalling in Drosophila?

Answer 4

Notch pathway signalling that spaces R8 photoreceptors in the drosophila eye disc morphogenetic furrow (development of eye)

Question 5

What is an example of synaptic signalling?

Answer 5

Neurons - they may a very small number of targets

Question 6

What is an example of paracrine signalling?

Answer 6

Hedgehog (Hh) expression = Decapentaplegic (Dpp) ligand expression - secreted by cells in the middle of Drosophila wing disc.

This activates downstream transcription factor Mad (red).

Question 7

Why do Hedgehog and Decapentaplegic require paracrine signaling?

Answer 7

As they are large proteins, therefore require paracrine signaling to cause the downstream effects necessary.

Question 8

What is an example of endocrine signaling?

Answer 8

Adrenaline (produced by adrenal glands) acts on adrenergic receptors to produce a range of physiological responses.

Question 9

What is an example of endocrine signaling in bees?

Answer 9

Queen produces pheromones that control hives of tens of thousands of workers

Question 10

What are 3 ways cells can respond to signaling?

Answer 10

• altered metabolism
• altered gene expression
• altered cell shape or movement

Question 11

Give an example of how metabolic enzymes can lead to altered metabolism? (think yeast metabolism)

Answer 11

There can be changes in yeast metabolism triggered by different sugars provided as energy source

Question 12

Describe how gene expression might be altered

Answer 12

Through gene regulatory proteins - expression of Iroquois family genes in the E12 mouse embryo

Question 13

Describe how cell shape or movement can be altered

Answer 13

Human neutrophil chasing signal given off by Saphylococcus aureus

Question 14

Describe how a paracrine signalling works

Answer 14

Extracellular signal molecule –> receptor protein –> intracellular signaling –> effector proteins

Question 15

What is a morphogen gradient?

Answer 15

a special case where the response of cell to a signal occur at specific thresholds

Question 16

Describe how a morphogenic gradient defines the anterior parts of the resulting embryo in Drosophila

Answer 16

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

Question 17

What 3 ways can cells respond to signalling?

Answer 17

• 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)

Question 18

Describe the formation of myeloproliferative neoplasms and what they are associated with`

Answer 18

A mutation in the negative regulatory domain of JAK2, which leads to overproduction of erythrocytes. Associated with >95% of blood cancer patients.

Question 19

Describe the formation of chronic myeloid leukaemia

Answer 19

Bcr-Abl fusion protein that causes sustained Abl tyrosine kinase expression by the Bcr promoter/enhancer region leading to CML

Question 20

What are 2 examples of how a lack of regulation of tyrosine kinase leads to disease?

Answer 20

• Myeloproliferative neoplasms
• Chronic Myeloid Leukaemia

Question 21

At what stages may a signalling pathway be regulated?

Answer 21

• Extracellular/ligand/receptor
• Intracellular/transduction of signal
• Effectors can ‘feedback onto their own pathway

Question 22

Give an example of how an effector might produce a positive feedback

Answer 22

Notch pathway lateral inhibition (produces a binary outcome)

Question 23

Give an example of how an effector may create a negative feedback

Answer 23

JAK/STAT pathway down regulation by SOCS negative regulator

Question 24

Why is it useful to alter the activity of a protein?

Answer 24

switching a protein on/off is more efficient than creating and destroying them.

Question 25

What are 2 ways to alter protein activity?

Answer 25

• signaling by phosphorylation (addition of phosphate group)
• signaling by GTP binding

Question 26

How are GTPase activity levels regulated?

Answer 26

Through modulating GAP (GTPase-Activating Protein) and GEF (Guanine Nucleotide Exchange Factor) levels

Question 27

What do GAPs do?

Answer 27

GTPase activating proteins - GTP to GDP through hydrolysis
- INactivating them

Question 28

What do GEFs?

Answer 28

Guanine Nucleotide Exchange Factor - GDP to GTP
- activating GTPases

Question 29

When are small GTPases active/inactive?

Answer 29

GTP bound - active
GDP bound - inactive

Question 30

What can occur when GTPases are active?

Answer 30

They can interact with their effector proteins and trigger specific cellular functions

Question 31

What are the 2 major groups of protein kinases?

Answer 31

• serine / threonine kinase
• tyrosine kinase

Question 32

What do protein kinases do?

Answer 32

Add phosphates

Question 33

Describe the role of Serine/Threonine kinase

Answer 33

• Serine <–> Phospho-serine
• Threonine <–> Phospho-threonine

Question 34

Describe the role of Tyrosine kinase

Answer 34

Tyrosine <–> phospho-tyrosine