Receptors and Signalling

Question 1

What is the purpose of membrane receptors?

Answer 1

Binding the signal or ligand

Producing a second signal / messenger which causes cellular response

Question 2

What are the three stages of bio signalling?

Answer 2

1. Reception
2. Transduction
3. Response

Question 3

How does intercellular communication work, in brief?

Answer 3

1. Upon reception of triggering stimulus the signal is transformed into a chemical or electrical messenger within the signalling cell
2. The messenger is secreted and transported to the target cell
3. In the target cell, the messenger is recognised, transmitted, and converted into a biochemical reaction

Question 4

What are the 2 different types of signalling and their relevant subtypes?

Answer 4

1. Direct (cell-to-cell signalling) via gap junctions (pressed together cells)
2. Chemical (sigalling by secreted molecules) which has three subtypes
   - Enocrine (widespread)
   - Paracrine (including synaptic)
   - Autocrine

Question 5

What is direct signalling?

Answer 5

A transfer of ions or small molecules from one cell to its neighbour cell

Allows electrical signal transduction through pores in the membrane (gap junctions)

Fastest mode of cell-to-cell communication

Question 6

What are connexons?

Answer 6

A transmembrane protein made of tightly packed hollow cylinders called connexins

They form a 3nm thin hydrophilic channel, with no leaks, to facilitate direct commuincation between cells of signallin molecules

Question 7

How does endocrine signalling worK?

Answer 7

1. Signal is produced by hormones from an endocrine gland
2. Signal travels throught the bloodstrream to distant cells
3. Cells receive the travelled signal through surface receptors (most protein andpeptide hormones) and intracellular receptors (steroid hormones)

Question 8

What are examples of endocrine signals / hormones?

Answer 8

Lipophilic molecules eg testosterone

Hydrophilic molecules eg plasma membrane receptors like insulin and glucagen

Question 9

How does paracrine signalling work?

Answer 9

1. Signals are produced similarly to hormones, but DO NOT enter blood circulation as they are rapidly destroyed by extracellular enzymes or bound to extracellular matrix (preventing widespread diffusion)
2. Signal travels to nearby cells in which the gradient of signal molecule received determines the outcome (exact distance uncertain)

Question 10

What is synaptic signalling and how does it work?

Answer 10

Special case of paracrine signalling

Involves synapses between originating cell and receiving cell and can ONLY occur between cells with synapses

Question 11

What is autocrine signalling?

Answer 11

Signal molecules are secreted by the target cell itself

Eg prostaglandins

Question 12

How do cells respond to signals?

Answer 12

1. Receptor protein receives signal
2. Undergoes conformational change eg haemoglobin
3. Launches series of biochemical reactions within the cell
4. Ultimate response can be altered gene expression, cell shape, or movement of metabolism etc

Question 13

What are the biochemcial reactions within a cell once a receptor protein receieves a signal?

Answer 13

1. Signal transduction cascades and amplifies the message

2. Multiple intracellular signals occur which can trigger synthesis of second messengers

Question 14

What are the different types of receptors and how they receive signals?

Answer 14

1. Ion-channel receptors = ligand-gated channels
2. Receptors with intrinsic or associated enzymatic activity
3. G protein-coupled receptors (GPCRs)

Question 15

How do receptors with intrinsic or associated enzymatic activity react when a signal is received?

Answer 15

1. Ligand activates the catalytic activity of the receptor

2. This activates an effector protein

Question 16

In brief, how does G-protein coupled receptors work?

Answer 16

1. Receptor is activated via ligand binding, resulting in conformational change
2. This activates the G-protein
3. G-protein activates an effector protein / enzyme to generate an intracellular second messenger

Question 17

In as much detail as possible, what is a G-protein and what happens when it activates?

Answer 17

G-protein = heterotrimeric proteins

1. In the inactive state, Ga is bound to GDP (off switch)
2. Interaction between Ga and stimulated receptor causes the release of GDP
3. GTP (on switch) binds to the empty site due to higher intracellular concentration
4. The GTP bound Ga has low affintiy to beta / gamma subunits, resulting in dissociation
5. GTP is quickly hydrolysed back to GDP - becomes inactive and stops the singal from continuing

Question 18

What is a second messenger?

Answer 18

A substance that is released in the cytoplasm following activation of a receptor

Relays information from the first messengers (hormones / signal molecules)

Is non-specific and generates a variety of responses in the cell

Question 19

What are key points about the second messenger cAMP?

Answer 19

Helps cell receive extracellular signals (adrenaline, glucagen etc)

Activates protein kinase

Phosphorylation of target proteins

Question 20

What does protein kinase do?

Answer 20

Selectively modifies other proteins by adding phosphate groups to themselves / other proteins when active

Opposed by phosphates which remove phosphate groups from specific phosphorylated proteins