cell signalling

Question 1

what is the significance of cell signalling?

Answer 1

1. cell signalling ensures that cellular activites occur in the right cells, at the right time and in proper coordination with other cells
2. this allows an organism to function as an integrated and coherent whole, consisting of a multitude of diverse tissues and organs, rather than a massive collection of independently functioning cells

Question 2

what are the steps in signal reception?

Answer 2

1. a signal is detected when a signal molecule binds to a specific receptor protein located at the cell’s surface or inside the target cell
2. ligand-receptor interaction between the signal molecule and the receptor protein is highly specific, as it binds to a specific complementary site on the target cell’s receptor to form a ligand-receptor complex
3. this causes the receptor protein to undergo a conformational change, often directly activating the receptor, enabling it to interact with other molecules in the cell

Question 3

what are the steps in signal transduction?

Answer 3

1. the formation of the activated ligand-receptor complex changes the formation of the receptor protein, initiating transduction
2. transduction often occurs via a multistep signal transduction pathway consisting of a series of relay molecules, which are usually proteins such as enzymes that operate in a specific sequence.
3. each protein in the pathway typically acts by altering the conformation of and hence activating or inhibiting the protein immediately downstream.
4. a phosphorylation cascade is formed, where relay proteins in a signal transduction pathway are sequentially phosphorylated, transmitting the signal received at the cell surface into the cell
5. transduction may also involve non-protein molecules that function as second messengers, which rapidly relay the signal from the cell surface into the cell interior via diffusion

Question 4

what are the steps in cellular response?

Answer 4

1. the regulation of one or more cellular activities may occur in the cytoplasm or may involve action in the nucleus
2. cytoplasmic responses involve changes in cell metabolism, including the regulation of enzyme activity such as activation of cytoplasmic enzymes or other proteins, and cytoskeletal arrangement
3. nuclear reponses involve changes in gene expression such as turning specific genes on or off in the nucleus, and hence synthesis of enzymes or other proteins

Question 5

what are the general characteristics of cell surface receptors?

Answer 5

1. cell surface receptors are present as transmembrane proteins embedded in the plasma membrane of target cells
2. cell surface receptors make up the majority of a cell’s signal receptors
3. cell surface receptors allow for hydrophilic molecules to bind to specific sites on receptor proteins, as they are unable to diffuse across the hydrophobic core of the cell surface membrane

Question 6

what is the action of protein kinases?

Answer 6

the action of protein kinases enables PK phosphorylates to add a phosphate group from ATP to a protein, thus activates them. these proteins are involved in multiple catalytic steps in a signal transduction pathway

Question 7

what is the action of protein phosphatases?

Answer 7

1. protein phosphatases enable PP dephosphorylate to dephosphorylate a protein molecule, thus inactivating them
2. this turns off the signal transduction pathway when the signal molecule is no longer present, allowing for protein kinases to be available for reuse

Question 8

what occurs in a phosphorylation cascade?

Answer 8

1. a signal molecule is transmitted by a cascade of sequential protein phosphorylation, each bringing with it a conformational change which results from the interaction of the newly added phosphate groups with charged or polar amino acids
2. this changes a protein from an inactive form to an active form

Question 9

what are second messengers?

Answer 9

1. second messengers are non-protein signal molecules, which include small, non-protein, water-soluble molecules or ions.
2. the two common second messengers are cyclic AMP and calcium ions

Question 10

what is the action of second messengers?

Answer 10

1. binding of the first messenger onto receptors stimulate an increase in the concentration of second messengers
2. the small and water-soluble second messengers can readily spread throughout the cytosol by diffusion.
3. as there is a large variety of relay proteins that are sensitive to the cytosolic concentration of second messengers, binding of second messengers to these proteins can alter the behaviour of relay proteins
4. second messengers enable cells to mount a large-scale, coordinated response following stimulation by a single extracellular signal molecule, stimulating a variety of cellular activities

Question 11

what is the structure of the G-protein linked receptor (GPLR)?

Answer 11

1. each G-protein linked receptor is made up of 1 polypeptide chain
2. the single polypeptide chain comprises seven alpha-helices spanning the cell surface membrane, connected by non-helical segments
3. hydrophobic interactions between the seven transmembrane alpha-helices result in a barrel-shape conformation for the receptor. hydrogen bonds and a highlt conserved disulfide linkage between the non-helical segments also stabilise the protein
4. the N terminus and 3 non-helical segments form the extracellular domain of GPLR. the seven alpha-helices form the membrane-embedded domain, while the C-terminus and 3 non-helical segments form the intracellular domain of GPLR. GPLR has different binding sites for the specific signal molecule and G protein

Question 12

how does the structure of the GPLR relate to its function?

Answer 12

1. hydrophilic amino acids form the inter-helical loops and N and C termini. this enables the extracellular and intracellular domains to be soluble in aqueous medium and also interact with water-soluble ligands and G-protein
2. hydrophobic amino acid residues are primarily found in the seven transmembrane helices, and between the alpha-helices and the hydrophobic fatty acid tails of membrane phospholipids. this enables the membrane-embedded domain to be stabilised and embedded within the membrane bilayer
3. extracellular and intracellular domain contains specific amino acids at the signal binding site. this enables the signal binding site to have specific 3D conformation that allows for interaction with a specfic ligand and the G-protein. this also results in a huge diversity of ligands that different GPLRs can bind to
4. the binding of ligand to GPLR causes a conformation change in protein, allowing it to interact with G-protein. this enables GPLR to initiate signal transduction pathways via activation of the G-protein

Question 13

what is the action of the GPLR?

Answer 13

1. the G protein mediates the passage of the signal from the membrane surface into the cell interior, by functioning as a molecular switch. the GPLR and G protein work together with the target protein
2. when the ligand binds to the GPLR, this causes a change in the receptor conformation, activating the GPLR.
3. with an increased affinity for the G protein, the cytoplasmic side of the GPLR binds an inactive G protein, causing a GTP to displace the GDP bound to the G protein
4. the activated G protein dissociates from the GPLR and diffuses along the membrane, binding to a target protein to alter the target protein activity.
5. this change initiates a cascade of signal transduction events by triggering the next step in the transduction pathway, most often the production of second messengers, which triggers a cellular response
6. GTP then hydrolyses the bound GTP, so that the G-protein is inactive again. the signal molecule has also dissociated from the GPLR, and the inactive G protein leaves the enzyme and returns to its original inactive state

Question 14

what is the action of the cyclic adenosine monophosphate (cAMP)?

Answer 14

1. adenylyl cyclase converts ATP to cyclic AMP in response to an extracellular signal molecule that binds to a GPLR
2. an extracellular molecule such as epinphrine binds to and activates a GPLR, which activates a specific G-protein
3. the active G-protein activates adenylyl cyclase, which catalyses the synthesis of many molcules of cAMP, boosting the concentration of cAMP by 20-fold.
4. the immediate effect of cAMP is usually the activation of a serine/threonine kinase called protein kinase A. this activated kinase then phosphorylates various other proteins
5. phosphodiesterase converts the cAMP to AMP very shortly after

Question 15

why does calcium ions function as a second messenger?

Answer 15

1. its concentration in the cytosol is normally much lower than the concentration outside the cell
2. a brief increase to the cytosolic concentration of calcium ions causes many cellular responses

Question 16

how is low cytosolic calcium ion concentration maintained?

Answer 16

1. calcium ATPase in the ER membrane sequester calcium ions from the cytosol into the ER lumen.
2. calcium ATPase in the plasma membrane actively pump calcium from the cytosol into the extracellular fluid
3. sodium calcium exchangers in the plasma membrane couples export of calcium ions with the FD of sodium ions into the cytosol
4. mitochondrial calcium ion pumps move calcium ions into the mitochondria

Question 17

how does inositol triphosphate stimulates the release of calcium from the ER?

Answer 17

1. a signal molecule binds to the receptor, leading to the activation of G protein and consequently phospholipase C.
2. phospholipase C cleaves a plasma membrane phospholipid known as PIP2. into diacylglycerol and inositol triphosphate.
3. DAG functions as a second messenger in other pathways
4. IP3 quickly diffuses through the cytosol and binds to an IP3 gated calcium channel in the ER membrane, causing it to open
5. calcium ions diffuses out of the ER, raising the cytosolic calcium level
6. calcium ions activate the next protein such as calmodulin in on or more signalling pathway, producing a cellular response.

Question 18

what are the general characteristics of receptor tyrosine kinases (RTK)?

Answer 18

1. RTKs are a major class of cell surface receptors that possess enzymatic activity
2. the part of the receptor protein extending into the cytoplasm functions as an enzyme known as tyrosine kinase, which catalyses the transfer of a phosphate group from ATP to tyrosine on a substrate protein
3. RTKs trigger more than one different signal transduction pathway from single ligand-binding event, and can thus activate several different cellular responses and display significant functional diversity

Question 19

what is the action of RTKs?

Answer 19

1. the signal molecule binds to a subunit of the RTK, resulting in receptor aggregation and dimerisation
2. dimerisation leads to the activation of the tyrosine kinase activity of the receptor, resulting in autophosphorylation
3. each tyrosine kinase domain adds a phosphate from an ATP molecule to a tyrosineon the tail of its own or the other polypeptide subunit
4. the RTK is fully activated, and binds cytoplasmic relay proteins, altering their activity, localisation or ability to interact with other intracellular signalling proteins. each relay protein recognises and binds to a specific phoshorylated tyrosine. the bound relay protein becomes activated by undergoing a conformational change
5. each activated relay protein triggers a transduction pathway