Principles Of Signalling

Question 1

Three ways for extracellular information to be transmitted across the membrane

Answer 1

1) Signals passively cross membrane
2) Ion channels
3) Transmembrane receptors

Question 2

How is information transferred inside the cell?

Answer 2

Changes in protein states
Small non-protein molecules

Question 3

Main challenges of cellular information processing:
(5 things)

Answer 3

Extracellular info must be transmitted across the membrane to induce a response
Cells must respond in a predictable, reproducible way to a given signal
Cells must be able to diversify signals
Cells must be able to respond to faint incoming signals
Cells must be able to process multiple signals and decide an output

Question 4

Specificity

Answer 4

Cells must respond in a predictable, reproducible way to a given signal

Question 5

Diversifying signals

Answer 5

More than one output

Question 6

Amplification

Answer 6

Cells must be able to respond to faint incoming signals

Question 7

Signal integration

Answer 7

Cells must be able to process multiple signals and decide an output

Question 8

Biggest challenge of the five?

Answer 8

Getting info from extracellular environment to the cell interior

Question 9

Membrane-permeable signal examples

Answer 9

Nitric oxide -> blood flow regulation
Oxygen -> gene transcription
Steroid and thyroid hormones -> gene transcription

Question 10

2 types of ion channel

Answer 10

Ligand-gated
Voltage-gated

Question 11

Ligand-gated ion channel ->

Answer 11

Electrical signalling (synapses)

Question 12

Voltage-gated ion channels ->

Answer 12

Electrical signalling/calcium signalling

Question 13

7 transmembrane receptors

Answer 13

G protein-coupled receptors (GPCRs)
Receptor tyrosine factors
Tyrosine kinases associated receptors
Receptor serine-threonine kinases
Receptor guanylate cyclase
Tyrosine phosphatase receptors
Death receptor

Question 14

What stimulates receptor tyrosine kinases?

Answer 14

Growth factors/insulin

Question 15

What stimulates tyrosine kinases associated receptors?

Answer 15

Cytokines

Question 16

What stimulates receptor serine-threonine kinases?

Answer 16

Transforming growth factor beta

Question 17

What stimulates receptor guanylate cyclase?

Answer 17

Atrial naturetic peptide

Question 18

What stimulates death receptors?

Answer 18

Tumour necrosis factor

Question 19

What does stimulation of GPCRs lead to?

Answer 19

Light-detection, taste, smell, autonomic responses

Question 20

What does stimulation of receptor tyrosine kinases lead to?

Answer 20

Gene transcription: proliferation

Question 21

What does stimulation of tyrosine kinases associated receptors lead to?

Answer 21

Gene transcription: immune response, inflammation

Question 22

What does stimulation of receptor serine-threonine kinases lead to?

Answer 22

Gene transcription: development

Question 23

What does stimulation of receptor guanylate cyclase lead to?

Answer 23

Homeostasis: blood volume/pressure

Question 24

What does stimulation of tyrosine phosphatase lead to?

Answer 24

Cell-cell adhesion responses? We aren’t sure yet

Question 25

What does stimulation of death receptors lead to?

Answer 25

Apoptosis

Question 26

The fate of activated receptors - down-regulation

Answer 26

Internalisation of the receptor-ligand complex; can be recycled to surface or degraded in lysosome

Question 27

The fate activated receptors - desensitisation

Answer 27

Involves blocking downstream signalling from activated receptor

Question 28

Information transfer inside the cell - proteins

Answer 28

There are 4 types of state changes of proteins that allow information to be transferred. These changes in state are interlinked

Question 29

Names of the 4 ways proteins can change state in info transfer

Answer 29

Post-translational modification Conformational change Binding/dissociation Localisation/concentration

Question 30

How is specificity of protein information transfer ensured?

Answer 30

Precise protein-protein interactions interlink ('wire') proteins in 'pathways'

Question 31

5 types of post-translational modification

Answer 31

a) change conformation b) promote protein binding c) prevent protein binding d) change subcellular localisation e) change proteolytic stability

Question 32

How can phosphorylation disrupt structure?

Answer 32

Phosphate modification can sterically or electrostatically disrupt interactions

Question 33

How can phosphorylation induce structure?

Answer 33

New phosphate group can form new electrostatic or H-bonding interactions, introducing new structure

Question 34

Long-range effects of phosphorylation - disruption

Answer 34

Phosphate group at the interface of a tertiary or quaternary interaction can disrupt the interaction

Question 35

Long-range effects of phosphorylation - ordering

Answer 35

Phosphorylation that creates a docking site for a phospho-recognition domain can result in new tertiary and quaternary interaction

Question 36

Examples of conformational changes in signalling - tertiary structure transitions

Answer 36

Hinge-bending Interdomain rearrangements

Question 37

Examples of conformational changes in signalling - quaternary structure transitions

Answer 37

Oligomerisation Reorganisation on monomers within an oligomer

Question 38

Small (non-protein) signalling mediators

Answer 38

Information carried by smaller, simpler molecules Signalling based on rapid changes in concentration and location in cell Highly mobile to move throughout the cell Can result in enormous amplification of signal