topic 10: cellular signaling

Question 1

How do yeast cells communicate with other cells?

Answer 1

yeast cells communicate with cells of the opposite mating type bu using mating-type specific receptors on the outside of their plasma membranes

Question 2

Where did signalling mechanisms first arise?

Answer 2

in prokaryotes

Question 3

What is Quorum Sensing?

Answer 3

the ability to detect and respond to cell population density by gene regulation
-formation of biofilms

Question 4

Short distance (local) signalling includes:

Answer 4

cell signals are passed through specialized cell junctions–> direct contact (gap junctions, plasmodesmata)

some signalling chemicals are released into the interstitial fluid and perceived by close cells

Question 5

What does PARACRINE signalling act on?

Answer 5

on nearby target cells ( growth factors)
-local (short distance) signalling

Question 6

What does SYNAPTIC signalling act on ?

Answer 6

on neurons
-local (short distance) signalling

Question 7

What is a type of LONG distance signalling?

Answer 7

HORMONES: made by one tissue and perceived by cells in another tissue in endocrine signalling

Question 8

What are the three stages of Signal Transduction? (RTR)

Answer 8

1. RECEPTION- signalling molecule binds to a protein receptor and makes it do certain things (change shapes, chemical modifications etc.)
   -plasma membrane
2. TRANSDUCTION- series of relay molecule carries the signal into the cell via signal transduction pathway
   -cytoplasm
3. RESPONSE- signal transduction triggers a response
   -in cytoplasm
   -gene expression
   -catalysis enzymes and metabolites
   -rearrangement of the cytoskeleton etc.

Question 9

How does receptor specific proteins work?

Answer 9

-receptor binds the signal through molecular interactions
-signalling molecule acts as a ligand
-ligand/receptor binding is specific. a specific signal molecule will only bind (and activate) on specific receptor protein

Question 10

Where can receptors be located?

Answer 10

plasma membrane as integral proteins
-G protein-couple receptors
-Receptor tyrosine kinases
-Ion channel receptors

OR cytoplasmic, responding to membrane-permeable signals inside of the cell

Question 11

What is G protein coupled receptors (GPCRS)?

Answer 11

a cell-surface transmembrane receptor that works with the help of a G protein (binds with GTP)
-7 transmembrane domains
-signalling molecule binds to the binding site out of the cell the domains shift a bit causing conformation changes of the GPCR loops inside the cell
-shifting reveals a site inside the cell that can bind proteins

Question 12

What happens when the G proteins malfunction?

Answer 12

G proteins associated with GPCRs can cause disease (bacterial infections)
-toxins interfere with G protein function, thus blocking signal transmission within the cell

Question 13

What are G protein coupled receptors composed of?

Answer 13

-specific GPCR which binds a specific ligand
-a G protein which can bind either GDP (OFF state) or GTP (ON state)
-an enzyme which transfers the signal to the signal transduction pathway

Question 14

Is GDP the “on” or “off” state?

Answer 14

“off”

Question 15

Is GTP the “on” or “off” state?

Answer 15

“on”

Question 16

What are the FOUR steps of GPCRs?

Answer 16

1. when GDP is bound to the G protein, G protein is inactive
2. appropriate ligand binds to the extracellular side of the receptor , receptor is activated and changes shape. On the cytoplasmic side inside cell, the G protein binds to the GPCR. GDP is released and GTP is loaded in, activating the G protein.
3. activated G protein dissociates from the receptor and binds and activates the enzyme
   -makes cyclic AMP (cAMP) as a secondary messenger.
   -initiates the signal transduction inside cell.
   -ligand binding is reversible and can happen many times.
4. After a while, G protein hydrolyses the GTP —> GDP + Pi. G protein now inactivated “off”, leaving the enzyme resulting in reduced enzyme function to make signal transduction components

Question 17

What is a LIGAND?

Answer 17

small molecule, ion, protein, signalling molecule

Question 18

How is smell and taste signalling done through GPCRs?

Answer 18

cAMP opens Ca 2+ or Na + channels to initiate nerve transduction

humans: 400 odorant GPCR
dogs: 1100 odorant GPCR

Question 19

What are Receptor Tyrosine Kinases (RTKs)?

Answer 19

plasma membrane receptors with enzymatic activity
-catalyses the transfer of phosphate groups from ATP to the amino acid tyrosine
-in “off state”, they are single proteins (monomers) that are embedded in the membrane by a single alpha helix
-ligand binding site is on OUTSIDE of cell

Question 20

What are the stages of Receptor Tyrosine Kinases (RTKs)?

Answer 20

1. ligand (such as a growth factor) binds to the receptors, allows two monomers to come together to form dimers (dimerization)
2. Dimerization activates the tyrosine kinase region on each monomer
   3.each tyrosine kinases adds a phosphate group from ATP molecule to a tyrosine on the large interior domain (tail)
   -this phosphorylation activates the receptor
3. area of cytoplasmic domains with the phosphorylated tyrosine acts as “docking sites” for relay proteins to bind and become activated
   -results in structural changes that activate relay proteins
   -each activated relay protein triggers a transduction pathway, leads to cellular response

Question 21

What are the basic cell functions the RTK regulate in humans?

Answer 21

1. Triggering cell division
2. Differentiation of cells into different cell types
3. Survival of a cell: apoptosis or not (cell death)

Question 22

What are the stages of Ligand-gated Ion Channels?

Answer 22

When a signalling ligand binds to a receptor the channels open or closes, allowing or blocking the flow of specific ions (such as Ca 2+ or Na+) through a channel in the receptor

1. the gate is closed when there is no ligand so ions cannot flow through it
2. When the ligand binds to the receptor, it changes shape and opens he channel, allowing ions to flow through via their concentration gradient.
3. ligand dissociates from the receptor, the channel reverts to its original shape and closes, blocking ions from flowing through

IMPORTANT IN NERVOUS SYSTEM!!

Question 23

What is Intracellular Receptor Signalling?

Answer 23

some ligands can cross the plasma membrane and bind to receptors in the cytosol, causing conformation change in the receptor

EXAMPLE: steroid hormone interacting with an intracellular receptor

1. steroid hormone aldosterone passes through the plasma membrane
2. aldosterone binds to a receptor proton in the cytosol, activating it
3. hormone-receptor complex enters the nucleus and binds to specific genes
4. the bound protein acts as a transcription factor, stimulating the transcription of the gene in mRNA
   5.the mRNA is translated into a specific protein

Question 24

What are transcription factors?

Answer 24

proteins that can bind DNA at specific nucleotide sequences and turn on the transcription of specific genes

Question 25

What is APOPTOSIS?

Answer 25

"programmed cell death" -results from Receptor Tyrosine Kinases -cellular agents will chop up and recycle cell bits (DNA, organelles etc.) by specialized vesicles. -cells shrink and becomes lobed 1. signal molecules from outside the cell can bind to the RTK and initiate a signal transduction pathway 2. genes ced-3 and ced-4 encode for the cell death proteins 3. when a cell death signal is received, it deactivates ced-9n protein, which no longer inhibits ced-4 4. ced-4 activated ced-3, which activated other enzymes that systematically deconstruct the cell

Question 26

What are the different pathways involved in apoptosis?

Answer 26

1. Mitochondrial proteins that are triggered to form holes in the outer mitochondrial membrane 2. External death signals and proceeds in the normal reception, transduction via relay proteins and response (death) 3. Internal "alarm" signals created by the nucleus when DNA is unrepairable and too compromised for the cell to undergo cell division

Question 27

Why are multistep signal transduction pathways advantageous?

Answer 27

1. amplifies the signal since each molecule involved can transmit the signal to numerous other molecule 2. more opportunities for control and coordination

Question 28

What are the steps in the Transduction multistep signal relay pathway?

Answer 28

Kinases are enzymes that phosphorylate molecules. When multiple kinases work together to send along a signal it is a phosphorylation cascade. 1. A relay molecule activates Kinase 1 2. active protein kinase 1 transfers a P from ATP to inactivate kinase 2 (thus activating it) 3. active kinase 2 than catalyses the phosphorylation (and activation) of kinase 3 4. active kinase 3 phosphorylates a protein that initiates cell response

Question 29

What are secondary messengers?

Answer 29

are small molecules (non-protein, water soluble molecules or ions) that help relay the signal -the ligand is considered the primary signal messenger -secondary messengers are readily available to the cell since they can diffuse throughout the cell

Question 30

What are some secondary messengers?

Answer 30

1. Cyclic AMP (cAMP) is often made by the GPCR- activated adeylyl cyclase 2. Calcium Ions can enter the cell through ligand gated ion channels and trigger cellular responses

Question 31

Describe the cAMP (secondary messenger) ?

Answer 31

1. first messenger binds to GPCR, activating it 2. Activated GPCR binds to G protein, which is then bound by GTP, activating the G protein 3. Activated G protein/ GTP binds to adenyl cyclase. GTP is hydrolyses activating adenyl cyclase. 4. Activated adenyl cyclase converts to ATP to cAMP 5. cAMP, a secondary messenger activates another protein, leading to cellular response.

Question 32

Describe the steps of Calcium Ions and Inositol Triphosphate (IP3)?

Answer 32

1. Signalling molecule binds to a receptor leading to activation of phospholipase C 2.Phospholipase C cleaves a plasma membrane phospholipid called PIP2 into DAG and IP3 3. DAG functions as a secondary messenger in other pathways 4. IP3 diffuses through he cytosol and binds to an IP3-gated Ca2+ channel in the ER, opening it 5. Ca2+ ions flow out of the ER, raising the concentration of cytosolic Ca2+ 6. Ca2+ ions activate the next protein in the one or more signalling pathways

Question 33

What type of ligands have the quickest triggering?

Answer 33

1:1 signal from receptor to the cellular response IS NOT quick enough to respond to changing conditions -dilute ligands have difficulty quickly triggering large cellular responses -direct signalling wouldn't work

Question 34

What is signal amplification?

Answer 34

at each step, MANY signalling molecules are activated, which activate many molecules on the next step and so on...

Question 35

Why are signalling pathway important?

Answer 35

-initiate gene expression (synthesizes proteins) -regulate metabolic pathways -open ion channels -regulate protein activity

Question 36

How do signalling pathways with a single response work?

Answer 36

- a specific ligand can activate a specific receptor in one cell type to give response 1

Question 37

How do signalling pathways with multiple responses work?

Answer 37

branched pathways: a specific ligand can activate a specific receptor in a different cell type to give response 2 and response 3 these response can be different ex. response 2 (regulation of enzyme activities) response 3 (transcription of specific genes)

Question 38

How do signalling pathways with cross talk and a single response work?

Answer 38

-two different ligand are activating two different receptors -activation of one can either increase or inhibit the response of the other pathway. CROSS TALK. 2 ligands activate 2 receptors, results in 1 response

Question 39

What do signal transduction pathways allow for (RAD) ?

Answer 39

1. Rapid signalling from dilute hormones to responses 2. Amplification of the signal 3. different cell types to respond/ interact to signalling differently

Question 40

What are SCAFFOLDING PROTEINS?

Answer 40

some pathways utilize these proteins to help simplify the relay pathways -can permentaly hold pathways and networks together to make for efficient design *less distance to travel *faster and more accurate EXAMPLE: brain signal transduction pathways are super complex and utilize these proteins!

Question 41

Can signalling pathways end?

Answer 41

YES!

Question 42

How do signalling pathways end?

Answer 42

termination of the signal transduction pathways can reduce or stop the cell response -unbound receptors revert to their inactive forms -GTPase activity of the G protein hydrolyses its bound GTP, converting it to GDP to turn off the G protein -cAMP converts to AMP via phosphodiesterase -protein phosphates inactive phosphorylated kinases and other proteins END: no more signal, no more cell response!