Lecture 8: Cell Communication || Intracellular Signalling

Question 1

How signalling molecules work depends on their what?

Answer 1

physical and chemical properties

Question 2

How do steroids and thyroid hormones act on intracellular receptors? Why is this?

Answer 2

Steroids and thyroid are lipophilic and are therefore carried into the blood attached to carrier protein. This is an equilibrium process and so some falls off the carrier protein. This can simply diffuse into the cell through the membrane. They can bind to receptors in the cytoplasm and then travel into the nucleus, or they go straight into the nucleus. It forms a complex and binds to the DNA to cause translation and generation of new proteins

Question 3

Steroid hormones can cause what effect in the cell?

Answer 3

it can cause the generation of proteins and that act as the primary response of the cell or they could act as transcription factors themselves.

Question 4

Explain the process of thyroid hormone signalling

Answer 4

T3 and T4 diffuse across the membrane into the cytoplasm of the cell. Here, T4 is often converted into T3. It than binds to a nuclear receptor (retinoid X receptor) to form a three part complex consisting of of the hormone, the receptor and a cofactor (attached to the receptor). These three things form a transcription factor which then changes transcription to increase metabolism

Question 5

While lipophilic things like steroids and thyroid hormones can just diffuse into the cell, how do amino acid and peptide hormones affect the cell?

Answer 5

because they are hydrophilic, they can’t just diffuse into the cell and therefore have to act via cell surface receptors
When the hormone arrives and it binds to to receptor and the intracellular machinery is activated (2nd messenger system)

Question 6

An example of these cell surface receptors is a ligand-gated ion channel/ionotropic receptor. Explain how these work

Answer 6

these are receptors where the ion channel is an integral part of the receptor
when the signal molecule binds, the ion channel opens and the ions can enter or leave the cell

Question 7

Give an example of a ionotropic receptor

Answer 7

the glutamate receptor

Question 8

Steroid hormone receptors are only found in the nucleus BECAUSE steroid hormone-receptor complex binds to DNA

Answer 8

the first statement is false and the second is true

Question 9

Another example of cell surface receptors are G protein coupled receptors such as Gs and Gi receptors. Explain what the difference between these is

Answer 9

Their names stand for stimulatory G protein coupled receptor and inhibitory G protein coupled receptor. This name refers to the stimulation of inhibition of the second messenger system, not the response of the whole cell.

Question 10

Another example of cell surface receptors are G protein coupled receptors such as Gs and Gi receptors. Explain how the Gs receptor works part 1

Answer 10

There is a G protein coupled receptor spanning the cell membrane and inside the membrane there is a g-protein consisting of three subunits (α, β, gamma). When the signal molecule binds the receptor and the G-protein become associated with each other. At this point, the GDP that was bound to the α subunit unbinds and is replaced by GTP. This splits the α and β/γ subunits and the α subunit can go on and do other things inside the cell.

Question 11

Another example of cell surface receptors are G protein coupled receptors such as Gs and Gi receptors. Explain how the Gs receptor works part 2

Answer 11

the activated α subunit of the stimulatory G protein activates adenylyl cyclase which converts ATP to cyclic AMP. Cyclic AMP activates protein kinase A which can go on to phosphorylate other things in the cell such as CREB inside the nucleus. This binds to the DNA and activates gene transcription

Question 12

Describe how Gq (G protein coupled receptors) work

Answer 12

These start of the same as the Gs and Gi proteins coupled receptors with the associated α, β and gamma subunits. When the GDP is replaced by GTP, the activated α subunit activates phosphorylase C. This generates IP3 and DAG. IP3 leaves the membrane and goes to the endoplasmic reticulum to open the Ca2+ channels which releases Ca2+ into the cytoplasm. DAG activates protein kinase C which goes on to phosphorylate proteins

Question 13

What are receptor tyrosine kinases? What is its role?

Answer 13

These are receptors which has tyrosine kinase as a part of the receptor. The role of this tyrosine kinase is to phosphorylate tyrosine on proteins to activate these proteins

Question 14

Describe how enzyme-linked receptors work

Answer 14

these are 2 subunit receptors and when the signal molecule binds they stabilise inside the interaction in the intracellular portion of the receptor to then activate enzymes and other proteins inside the cell

Question 15

Give an example of an enzyme linked receptor

Answer 15

a tyrosine kinase-associated receptor

Question 16

What is a tyrosine kinase-associated receptor? What type of receptor is it?

Answer 16

this is when the tyrosine kinase is associated with the receptor. An example of this is a JAK kinase which can phosphorylate proteins inside the cell

Question 17

Another broad class of signalling receptor is regulated intermembrane proteolysis. Describe how this works

Answer 17

This is when the signalling molecule binds to allow the cleavage of the protein that it binds to via a metalloproteinase. Part of this molecule goes into the cell to become second messenger. It translocates into the nucleus, acting as a transcription factor and changing the transcription of genes. Eventually new proteins are created to increase or decrease the output of the cell

Question 18

What are eiscanoid receptors?

Answer 18

These are similar to regulated intermembrane proteolysis but instead of it breaking down proteins, it breaks down fats. When the signalling molecule binds, it becomes activated and now the activated receptor activates phospholipase A2 to cause the breakdown of lipids to arachidonic acid to enter the cyclooxygenase pathway producing a number of things such as prostaglandins which are involved in maintaining the vascular tone crucial for birth

Question 19

Explain how gaseous neurotransmitters affect cells, using NO as the example. Explain how NO is synthesised

Answer 19

These just diffuse to all neighbouring cells and are not necessarily in the synaptic cleft. An example of this is NO. Arginine is converted to citrulline in the presynaptic terminal via the enzyme nitric oxide synthase and NO is a byproduct of this reaction. NO diffuses into neighbouring cells and it does things such as activate soluble guanylyl cyclase to convert GTP to cyclic AMP.

Question 20

What are cys-loop receptors? What type of receptor are they? What are the different kinds?

Answer 20

These are also examples of ionotropic receptors but these have 5 subunits and 4 transmembrane domains. Depending on the subunits, there are different types of receptors for things like GABA, glycine, serotonin, ACh and purines.

Question 21

Explain how glutamate is synthesised, stored, secreted and reabsorbed.

Answer 21

Glutamate is synthesised in the axon terminal of the presynaptic terminal. It is converted from glutamine via the enzyme glutaminase. It is then packaged into vesicles in the presynaptic terminal. Because it needs to go up its concentration gradient to get into the vesicles, this requires energy. This energy comes from the conversion of ATP to ADP and this aids vGLUT to pump glutamate into the vesicles. When an action potential arrives in the presynaptic terminal and Ca2+ enters the cell, this stimulates the release of glutamate from the vesicles. The vesicles are released at the synaptic cleft. The glutamate is then recycled by a neighbouring glial cell. These cells express excitatory amino acid transporters EAAT1 and EAAT2 and these mop up any extra glutamate in the synaptic cleft. In this glial cell, glutamate is converted to glutamine by glutamine synthase and then it is picked up back into the postsynaptic cell by the EAAT5 receptor.

Question 22

Describe the glutamate receptor

Answer 22

The glutamate receptor is an ionotropic receptor because the ion channel is an integral part of the receptor. This receptor has four subunits and three submembrane domains. Depending on the makeup of these subunits, there are different types. These include NMDA, AMPA and kainate receptors.