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BIOL 1020 FINAL > topic 10: cellular signaling > Flashcards

topic 10: cellular signaling Flashcards

1
Q

How do yeast cells communicate with other cells?

A

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

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2
Q

Where did signalling mechanisms first arise?

A

in prokaryotes

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3
Q

What is Quorum Sensing?

A

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

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4
Q

Short distance (local) signalling includes:

A

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

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5
Q

What does PARACRINE signalling act on?

A

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

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6
Q

What does SYNAPTIC signalling act on ?

A

on neurons
-local (short distance) signalling

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7
Q

What is a type of LONG distance signalling?

A

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

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8
Q

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

A
  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.
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9
Q

How does receptor specific proteins work?

A

-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

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10
Q

Where can receptors be located?

A

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

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11
Q

What is G protein coupled receptors (GPCRS)?

A

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

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12
Q

What happens when the G proteins malfunction?

A

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

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13
Q

What are G protein coupled receptors composed of?

A

-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

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14
Q

Is GDP the “on” or “off” state?

A

“off”

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15
Q

Is GTP the “on” or “off” state?

A

“on”

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16
Q

What are the FOUR steps of GPCRs?

A
  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
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17
Q

What is a LIGAND?

A

small molecule, ion, protein, signalling molecule

18
Q

How is smell and taste signalling done through GPCRs?

A

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

humans: 400 odorant GPCR
dogs: 1100 odorant GPCR

19
Q

What are Receptor Tyrosine Kinases (RTKs)?

A

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

20
Q

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

A
  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
21
Q

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

A
  1. Triggering cell division
  2. Differentiation of cells into different cell types
  3. Survival of a cell: apoptosis or not (cell death)
22
Q

What are the stages of Ligand-gated Ion Channels?

A

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!!

23
Q

What is Intracellular Receptor Signalling?

A

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
24
Q

What are transcription factors?

A

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

25
Q

What is APOPTOSIS?

A

“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
26
Q

What are the different pathways involved in apoptosis?

A
  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
27
Q

Why are multistep signal transduction pathways advantageous?

A
  1. amplifies the signal since each molecule involved can transmit the signal to numerous other molecule
  2. more opportunities for control and coordination
28
Q

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

A

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
29
Q

What are secondary messengers?

A

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

30
Q

What are some secondary messengers?

A
  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
31
Q

Describe the cAMP (secondary messenger) ?

A
  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.
32
Q

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

A
  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

  1. DAG functions as a secondary messenger in other pathways
  2. IP3 diffuses through he cytosol and binds to an IP3-gated Ca2+ channel in the ER, opening it
  3. Ca2+ ions flow out of the ER, raising the concentration of cytosolic Ca2+
  4. Ca2+ ions activate the next protein in the one or more signalling pathways
33
Q

What type of ligands have the quickest triggering?

A

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

34
Q

What is signal amplification?

A

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

35
Q

Why are signalling pathway important?

A

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

36
Q

How do signalling pathways with a single response work?

A
  • a specific ligand can activate a specific receptor in one cell type to give response 1
37
Q

How do signalling pathways with multiple responses work?

A

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)

38
Q

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

A

-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

39
Q

What do signal transduction pathways allow for (RAD) ?

A
  1. Rapid signalling from dilute hormones to responses
  2. Amplification of the signal
  3. different cell types to respond/ interact to signalling differently
40
Q

What are SCAFFOLDING PROTEINS?

A

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!

41
Q

Can signalling pathways end?

A

YES!

42
Q

How do signalling pathways end?

A

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!

BIOL 1020 FINAL (5 decks)

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