TOPIC J: CELL SIGNALLING

Question 1

What is contact dependent cell signalling?

Answer 1

Cells may communicate by direct contact between cells.
- cell junctions
in both plants and animals cells may communicate via cell junctions, where cytoplasms of adjacent cells are connected directly. Signal molecules dissolved in cytosol can pass freely between adjacent cells.
- cell-cell recognition
In animals, cell may communicate between membrane-bound molecules on the CSM.

Question 2

What is paracine signalling?

Answer 2

Numerous cells can simultaneously receive and respond to the molecules of growth factor produced by a single cell in their vicinity .

Question 3

What is synaptic signalling?

Answer 3

Neurotransmitters diffusing across synapses between neurons.

Question 4

Endocrine Signalling

Answer 4

A form of long distance signalling.
Signal molecules, known as hormones are secreted into the circulatory system to act on distant target cells.
Specialised animal cells release hormone molecules into blood vessels of the circulatory system to other parts of the body, where they reach target cells that can recognise and respond.

Question 5

What is ligand receptor interaction?
(shape, change)

Answer 5

The ligand/signal molecule is complementary in shape to a specific binding site on the receptor and attaches itself there.
The binding of the ligand to the receptor induces a conformational change in membrane bound receptor or dimerisation of two membrane bound receptors. This change in shape activates the receptor, triggering downstream signalling pathways.
Signal molecules are large and/or hydrophilic. A large class of ligand molecules cannot pass through the CSM of the target cell.
The receptor proteins for these signal molecules have to lie in the CSM of the target cell and relay the message across the membrane.

Question 6

What are cell surface receptors?

Answer 6

A cell surface receptor is usually a transmembrane protein embedded in the cell surface membrane of the target cell. It allows the cell to receive the signal coming from outside the cell and respond to it.

Question 7

What are ion-channel receptors?

Answer 7

A ligand gated ion channel is a type of membrane bound receptor.
When a ligand binds to the extracellular side of the receptor, the gate opens or closes, allowing or blocking the flow of specific ions, such as Na+ or Ca2+, through a channel in the receptor.

Question 8

What is a G protein-linked receptor (GPLR)?

Answer 8

The G-protein linked receptor is closely associated with a G-protein.
G protein is a protein that binds to guanosine triphosphate (GTP) or (GDP).
Structure:
Single polypeptide chain with 7 hydrophobic transmembrane a-helixes
Has an extracellular ligand binding site and an intracellular protein binding site.

Question 9

How does the G protein-linked receptor work?

Answer 9

The GPLR is inactive when not bound to ligand. The G protein is inactive when bound to GDP. When the ligand binds to extracellular side of GPLR, the receptor is activated inducing it to change its conformation.
The cytoplasmic side of the receptor then binds an inactive G protein, causing the G protein to exchange its bound GDP for GTP.
The G protein is activated and dissociates from the receptor. Activated G protein binds to an enzyme, activating it. Once activated, the enzyme triggers signal transduction leading to cellular response.
Once signal molecule is absent, GTP is hydrolysed back into GDP by the GTPase enzyme found in the G protein subunit. The G protein thus dissociates from the enzyme and returns to its inactive form. The signal is switched off.

Question 10

What is the tyrosine kinase receptor and its structure?

Receptor tyrosine kinases (RTKs)

Answer 10

One RTK complex may activate ten or more different signal transduction pathways and cellular responses helping the cell to regulate and coordinate several cell activites simultaneously.
Structure:
Is a single polypeptide chain with a single transmembrane a-helix.
Has an extraceullar ligand binding site
Has an intracellular tail that functions as tyrosine kinase and also contains a number of tyrosine amino acid residues.
A tyrosine kinase is an enzyme that catalyses the transfer of phosphate groups from ATP to the tyrosine residues on substrate protein, activating it.

Question 11

How does a receptor tyrosine kinase work?

Answer 11

Before a ligand binds, the receptor exist as individual RTK monomers.
The binding of a ligand to the extracellular binding sites of RTKs causes two RTK proteins to come together in the membrane, forming a dimer.
Dimerisation activates the tyrosine kinase function found in the intracellular tails of RTK.
Each tyrosine kinase adds phosphates group from ATP molecules to the tyrosine residues on the tail of the RTK protein by autophosphorylation. The activated RTK will trigger the assembly of relay proteins on the receptor tails.
Each relay protein undergo a structural change, activating them, each activated relay protein triggers a signal transduction pathway, leading to a cellular response.

Question 12

What are signal molecules?

Answer 12

A smaller, class of ligands consisting molecules that are able to diffuse across the CSM
The receptor for these signal molecules have to lie in the interior of the target cell and when bound to their ligands they generally act as gene regulatory proteins.

Question 13

What are intracellular receptors?

Answer 13

Intracellular receptors are located either in the cytosol or in the nucleus of target cells.
To reach an intracellular receptor, the ligand has to pass through the target cell’s surface membrane. Thus the signal molecule must be small and hydrophobic to pass through the hydrophobic core of the membrane.

Question 14

What is signal transduction and how does it occur?

Answer 14

Transduction converts the signal to a form that can bring about a specific cellular response. The signal transduction pathway often requires a sequence of changes in a series of different relay molecules in a multistep pathway.
Signal transduction occurs via two main ways, protein phosphorylation in a phosphorylation cascade, and release of second messengers. Such pathways also allow for signal amplification.

Question 15

What is phosphorylation cascade?

Answer 15

The activated receptor activates a relay molecule, which activates another relay molecule and so on, until the molecule that produces the final cellular response is activated.
Many of the relay molecules in signal transduction pathway are protein kinases and they act on other protein kinases in the pathway.
Each activated protein kinase will initiate a sequential phosphorylation and activation of other kinases, resulting in a phosphorylation cascade.
Relay molecules are usually activated when they are phosphorylated and deactivated when they are dephosphorylated.

Question 16

What are second messengers?

Answer 16

Not all relay molecules in the signal transduction pathway are proteins. Second messengers are small, non protein, water-soluble molecules or ions that relay signals received at receptors on the cell surface to target molecules in the cytosol.
As second messengers are small and water-soluble, they can readily diffuse throughout the cell. They greatly amplify the strength of the signal.

Question 17

What is cyclic adenosine monophosphate (cAMP)?

Answer 17

An enzyme embedded in the cell surface membrane, adenylyl cyclase, when activated by the G protein, can convert many ATP to cAMP molecules.
The cytosolic concentration of cAMP is elevated twenty-fold in a matter of seconds amplifying the signal the cytoplasm.
It does not persist for long in the absence of the hormone, because another enzyme, called phosphodiesterase, converts the cAMP to AMP, resulting in signal termination.

Question 18

What is signal amplification?

Answer 18

If some of the relay molecules in a pathway transmit the signal to multiple molecules of the next component in the series, the result can be a large number of activated molecules at the end of the pathway.
In other words, a small number of extracellular signal molecules can produce a large cellular response.

Enzyme cascades amplify the cell’s response to a signal. At each catalytic step in the cascade, the number of activated products is much greater than those in the preceding step.

Question 19

What is a cellular response?

Answer 19

Regulation of protein activity
Regulation of protein synthesis by turning specific gene expression on or off in the nucleus
Regulation of enzyme activity
Rearrangement of the cytoskeleton in the cell
Cell death

Question 20

What is signal termination?

Answer 20

Dissociation of ligand from receptor when concentration of signal molecules drops. Receptor reverts to its inactive form.
The GTPase activity intrinsic to a Gprotein hydrolyses its bound GTP to GDP.
Protein phosphatases inactivate protein kinases by dephosphorylation
Phosphodiesterase converts cAMP to AMP.

Question 21

What are the advantages and significance of a cell signalling system?

Answer 21

Specificity in the ligand-receptor interaction allows signal molecule to elicit responses in specific target cells.
The ability of a signal molecule to activate many different target cells simultaneously allows for regulation and control of response.
Signal amplification allows for one signal moleq to trigger a large cellular response.
One signal molecule can activate many signal transduction pathways to trigger numerous cellular reactions simultaneously.
The binding of signal moleq to receptor at cell surface membrane can result in activation of gene transcription in the nucleus.

Question 22

How does differential gene expression affect the cellular response?

Answer 22

A cell may or may not express a receptor for a particular signal molecule.
Different cell types may have different cell surface receptors that recognise the same signal molecule.
The expression of proteins involved in intracellular signal transduction pathways may vary in different cell types.
The expression of proteins that are controlled by signal transduction pathways may vary in different cell types.

Question 23

What is the glucagon and GPLR signalling pathway?

Answer 23

1. During ligand-receptor interaction, binding of glucagon to extracellular side of GPLR activates the receptor and causing it to change its conformation.
   The cytoplasmic side of the receptor then binds an inactive G protein, causing G protein to exchange its bound GDP for GTP.
   The G protein is activated and dissociates from the receptor. Activated G protein binds and activates adenylyl cyclase, which catalyses the conversion of large numbers of ATP to cAMP.
2. cAMP, a second messenger, binds and activates a large number of protein kinase A (PKA)
   Each activated protein kinase will initiate a sequential phosphorylation and activation of other kinases, resulting in a phosphorylation cascade. Each activated kinase is able to activate a large number of the next kinase.
   At each catalytic step in the cascade, the number of activated product is always greater than those in the preceding step, resulting in signal amplification.
   The final activated protein is glycogen phosphorylase.
3. During cellular response, a large number of glycogen phosphorylase is activated, which will catalyse the breakdown of glycogen into glucose.
   It includes an increased synthesis or activity of enzymes involved in glucose synthesis, a metabolic pathway that results in the generation of glucose from non-carbohydrate carbon substrates such as lactate, glycerol and glucogenic amino acids.
4. Glucagon is released from receptor, GTPase activity intrinsic to a G-protein hydrolyses is bound GTP to GDP.
   Phosphodiesterase converts cAMP to AMP.

Question 24

What is the first step of the insulin and RTK signalling pathway?

Answer 24

During ligand-receptor interaction, binding of insulin to extracellular binding sites of RTK causes 2 RTK proteins to form a dimer.
Dimerisation activates the tyrosine kinase function found in the intracellular tails of RTK. Tyrosine kinase adds phosphate group from ATP molecule to the tyrosine residues on the tail of the other RTK protein by autophosphorylation.

Question 25

What is the insulin and RTK signalling pathway second step?

Answer 25

During signal transduction, the activated RTK will trigger the assembly of relay proteins on the receptor tails, activating them.
Activated relay proteins further recruit and activate other downstream relay molecules and protein kinases.
Each activated protein kinase will initiate a sequential phosphorylation and activation of other kinases, resulting in a phosphorylation cascade.
At each phosphorylation step, each activated kinase is able to activate a large number of the next kinase.
The number of activated product is always greater than those in the preceding step, resulting in signal amplification.

Question 26

What is the cellular response stage in the insulin RTK pathway?

Answer 26

Activated relay proteins cause vesicles embedded with glucose transporters to move to the cell surface membrane and fuse with it, thus inserting the transporters into the CSM.
Large number of glycogen synthase is activated catalyses the synthesis of glycogen from glucose.
Decrease activity or synthesis of enzymes involved in glycogenolysis and gluconeogenesis.

Question 27

What is the signal termination in the insulin pathway?

Answer 27

Insulin is released from receptors, the tyrosine residues are dephosphorylated by phosphatases and dimer dissociates back into individual RTK proteins.
Protein phosphatases inactivate protein kinases by dephosphorylation.