The Need to Communicate II: How Cells Talk to Each Other

Question 1

What does a membrane look like?

Answer 1

A phospholipid bilayer with receptors that go through and are “stuck” to the membrane

Question 2

Cell-surface receptor

Answer 2

Cell-surface receptors are membrane-anchored proteins that bind to ligands on the outside surface of the cell. In this type of signalling, the ligand does not need to cross the plasma membrane, So many different kind of molecules (including larger, hydrophilic ones) may act as ligands.

Question 3

How many domains does a cell surface receptor have?

Answer 3

Three domains

Question 4

Describe the three domains

Answer 4

A typical cell-surface receptor has three different domains, or protein regions: an extracellular (“outside of the cell”) ligand-binding domain, a hydrophobic domain extending through the membrane and an intracellular (“inside of the cell”) domain, which often transmits a signal.

Question 5

What type of cell surface receptors are there?

Answer 5

Ligand-gated channel
G-Protein Coupled Receptors

Question 6

Ligand-gated channel

Answer 6

Neurotransmitters (ligand) binds to the receptor and opens the channel allowing the ions Ca2+ to pass through.
Voltage-gated ligand channel open and close in response to a change in voltage (potential difference).

Question 7

G-Protein Coupled Receptors

Answer 7

G Protein-coupled receptors (GPCRs) are a large family of cell surface receptors that share a common structure and method of signalling. The members of the GPCR family and all have seven different protein segments that cross the membrane, and they may transmit signals inside the cell through a type of protein called a G protein.
When its ligand is not present, a G protein-coupled receptor waits at the plasma membrane in an active state. For at least some types of GPCRs, the inactive receptor is already docked to its signalling target, a G protein.

Question 8

When is a G-Protein Coupled Receptor “on”?

Answer 8

A G protein attached to GTP is active, or “on”

Question 9

When is a G-Protein Coupled Receptor off?

Answer 9

A G protein that is bound to GDP is inactive, or “off”

Question 10

Structure of G proteins and GPCRs

Answer 10

The G proteins that associate with GPCRs are a type made up of three subunits, known as heterotrimeric G proteins. When they’re attached to an inactive receptor, they’re in the “off” form (bound to GDP).

Question 11

How does a G protein coupled receptor works?

Answer 11

When a signalling molecule binds to the G protein-coupled receptor, the G protein alpha subunit exchanges GDP to GTP.
The alpha subunit dissociates from the beta and gamma units and triggers a cellular response.
GTP is hydrolysed to GDP, and the signalling molecules comes off of the receptor.
The alpha subunit comes back together with the receptor and the beta and gamma subunits.

Question 12

Types of GPCRs

Answer 12

Gs = stimulates adenylate cyclase.
Gi = inhibits adenylate cyclase
Gq = Activates phospholipase C

Question 13

How do Gs GPCRs work?

Answer 13

Gs Ligand A receptor stimulates adenylate cyclase which converts ATP to cyclic AMP and that gets changed by phosphodiesterase to AMP which changes inactive PKA (inactive protein kinase) and then active protein kinase A is able to phosphorylate a protein.

Question 14

How do Gi GPCRs work?

Answer 14

Ligand B is a Gi GPCRs that inhibits adenylate cyclase.
cAMP acts as a secondary messenger as the protein that binds to the ligand can’t enter the cell so cAMP is used as the intracellular signal.

Question 15

Enzyme-linked receptors

Answer 15

Enzyme-linked receptors are cell-surface receptors with intracellular domains that are associated with an enzyme. In some cases, the intracellular domain receptor is actually an enzyme that can catalyse a reaction. Other enzyme-linked receptors have an intracellular domain that interacts with a domain.

Question 16

Receptor Tyrosine Kinase

Answer 16

Receptor tyrosine kinase (RTKs) are a class of enzyme-linked receptors found in humans and many other species. A kinase is just a name for an enzyme that transfers phosphate group to a protein or other target, and a receptor tyrosine kinase transfers phosphate groups specifically to the amino acid tyrosine.

Question 17

How does RTK signalling work?

Answer 17

In a typical example, signalling molecules first bind to the extracellular domains of two nearby receptor tyrosine kinases. The two neighbouring receptors then come together or dimerise. The receptors then attach phosphates to tyrosine’s in each others’ intracellular domains. The phosphorylated tyrosine can transmit the signal to other molecules in the cell.

Question 18

Insulin Receptor

Answer 18

1. Insulin binds
   
   2. Tyrosine Kinase activation
   3. Signalling molecules
   4. Translocate GLUT4 transporters
   5. Glucose uptake
   6. Protein synthesis
   7. Cell survival
   8. Proliferation

Question 19

Intracellular Receptors

Answer 19

Intracellular receptors are receptors proteins on the inside of the cell, typically inside the cytoplasm or nucleus. In most cases, the ligands of intracellular receptors are small, hydrophobic molecules, since they must be able to cross the plasma membrane in order to reach their receptors. For example, the primary receptors for hydrophobic steroid hormones, such as the sex hormones estradiol (an oestrogen) and testosterone, are intracellular.

Question 20

Nuclear receptors

Answer 20

Hormones like the steroid hormones are lipid soluble and can diffuse through the plasma membrane
Inside the cell they bind to their receptors causing a confirmational change.
The confirmational change allows a dimer to form
Dimer can then enter the nucleus.
The dimer binds to recognition sites on DNA and triggers (sometimes inhibits) transcription of specific genes.

Question 21

Endocrine Signalling

Answer 21

When cells need to transmit signals over long distances, they often use the circulatory system as a distribution network of messages they send. In long-distance endocrine signalling, signals are produced by specialised cells and released into the bloodstream, which carries them to the target cells in distant parts of the body. Signals that are produced in one part of the body and travel through the circulation to reach far-away targets are known as hormones.

Question 22

Paracrine

Answer 22

Paracrine means a cell’s target cell is acting on the receptor of a target cell that is a neighbouring cell.

Question 23

Autocrine

Answer 23

Autocrine means a cell secretes a hormone that acts on a receptor on itself.

Question 24

Examples of paracrine

Answer 24

Example of paracrine is nitric oxide: Local vasodilator released from endothelial cells

Question 25

Example of autocrine

Answer 25

Example of autocrine is prostaglandins: An inflammatory mediator.

Question 26

Direct Communication

Answer 26

Tight junction prevents the passage of molecules.
Desmosomes joins cells together
Gap junctions allow cell communication to happen.

Question 27

Tight Junctions

Answer 27

Form a belt around the cell, anchoring it to neighbouring cells.
Not attached to the cytoskeleton.
The belt stops membrane proteins moving past it
And stops molecules diffusing across the tissue.

Question 28

What are the two main functions of tight junctions?

Answer 28

Fence function and Gate function

Question 29

Describe fence and gate function

Answer 29

The tight junction can function as a gate by regulating paracellular transport between cells.
The tight junction can act as a fence, preventing apical cell membrane proteins from transporting to the basolateral surface and vice versa.

Question 30

Juxacrine Signalling

Answer 30

Juxacrine signalling is a form of cell signalling which occurs in cells that are close in contact with each other.
Not required to release signalling molecules to the extracellular space.
There is a direct cell contact
Examples are gap junctions in animals and plasmodesmata in plants
No diffusion of signalling molecules.

Question 31

How does juxacrine work?

Answer 31

Channels or bridges between cells formed from connexins
They allow small molecules and ions to pass between cells
So small chemical and electrical signals can pass through them
This is how electrical signals pass through smooth muscle.

Question 32

Desmosomes

Answer 32

Anchor cells together
Are attached to cytoskeleton
Cadherins form the link between the “plaques” in the individual cells.