Topic 8 - Cell communication Flashcards

1
Q

How do yeast cells communicate?

A

mating factor

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2
Q

An example of contact-dependant signalling? deets

A

nerve cell differentiation in fruit fly
destined neuronal cell inhibits surrounding cells from also becoming neuronal cells
uses inhibitory signal (delta) & receptor protein (notch)

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3
Q

Know hormones in table 16.1 - 1 MCQ to be had!

A

also on slide 10

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4
Q

The cells response to a signal depends upon which 3 factors?

A
  1. receptor
  2. signal transduction proteins present in the target cell
  3. genetic programming of cell
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5
Q

T or F - The same signal molecule can induce different responses in different target cells eg.

A

true -
Heart muscle: ACh -> receptor1 -> decease HR & force
Salivary: ACh -> receptor1 -> ++secretion
Skeletal muscle: ACh -> receptor2 -> ++contraction

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6
Q

An animal cell depends on multiple extracellular signals. explain how eg?

A

different cells can have different receptors & in many combinations that trigger different responses
eg. survival signals (receptors) + division signals => cell grow & divide
no survival signal => apoptosis

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7
Q

Extracellular signals that involve gene expression take how long?

A

mins to hrs

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8
Q

Extracellular signals that involve modify existing proteins/enzymes take how long?

A

secs to mins

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9
Q

Nuclear receptors include…? why are they referred to as this?

A

both, cytosolic and nuclear receptors

Because, when activated by hormone binding, they act as transcription regulators in the nucleus

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10
Q

Name the intracellular signalling molecules

Which one crosses as the neutral -COOH/NH2 species?

A

steroids (& other small hydrophobic ones)

  • cortisol
  • estradiol
  • testosterone
  • thyroid hormones (thyroxine) - neutral
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11
Q

How do steroid hormones exert their intracellular effects? eg.

A

by binding and activating the nuclear receptor protein -> nucleus -> activate or repress transcription of specific genes

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12
Q

Some dissolved gasses can cross plasma membrane & activate intracellular enzymes directly. Name one & give example…

A

nitric oxide (NO - synthesised from arginine) -> released by endo cells of blood vessels upon ACh stimulation -> rapid diffusion of NO thru plasma membrane -> smooth muscle cells -> binds to guanylyl cyclase -> cGMP -> vessel relaxes -> dilate -> ++blood flow (5 - 10 secs)

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13
Q

example of NO synthetic drug that doe this?

A

viagra -> blocks CGMP phosphodiesterase -> ++cGMP

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14
Q

Which molecules cannot cross the plasma membrane & must bind to cell surface extracellular receptors?

A

proteins, peptides, small, highly water-soluble molecules

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15
Q

How can extracellular signals often activate intracellular signal transduction pathways? flow chart is good. figure 16-12 (slide 25)…

A

extracellular signalling molecule -> receptor protein (transmembrane receptor) -> intracellular signalling molecules (relay analogy) -> effector proteins (eg. metabolic enzyme or transcription regulator) -> cell responses (eg. altered metabolism & altered gene expression)

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16
Q

The components of these intracellular signaling pathways perform one or more crucial functions. List & describe them.

A

Relay - relay signal & help spread it thru cell
Transduce & amplify - make signal stronger (via 2nd messengers) so few extracellular signal -> large intracellular response
Integrate - receive signals from more than one intracellular signaling pathway & integrate them before passing ‘em on
Distribute - distribute the signal to more than one signaling pathway or effector protein

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17
Q

Some proteins can act as molecular switches. What are they? on/off triggers?

A

Phosphorylation: on via protein kinase, off via protein phosphotase
GTP-binding proteins: on GTP bound, off GDP bound

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18
Q

What are the 3 classes of membrane receptors?

A
  1. Ion-channel-coupled receptors
  2. G-protein-coupled receptors (GPCRs)
  3. Enzyme coupled receptors
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19
Q

Ion-channel-coupled receptors. 3 correct statements about ‘em…

A
  1. open or close in response to binding of ligand to the receptor
  2. Also called transmitter-gated ion channels
  3. Activation alters membrane potential → signal
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20
Q

What number % are human genes are GPCRs?

A

4% of human genes (>800 genes known)

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21
Q

GPCRs are coupled to …? subunits…?

A

a trimeric G-protein with 3 subunits: alpha, beta & gamma

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22
Q

Stimulation of GPCRs Activates G-Protein Subunits. Explain using diagram how it works. include activation & inactivation steps. all players involved…

A

Figure 16.17 & 16.18 (textbook)

movie 16.2 - must know these mechanisms well!

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23
Q

The G-protein switch demonstrates a general principle of cell signaling mentioned earlier: the mechanisms that shut a signal off are as important as the mechanisms that turn it on. Describe a condition that fucks this mechanism leading to pathology. (not super important but good to understand and fairly easy to remember)

A

Cholera - a bacterium that multiplies in the intestine, where it produces a protein called cholera toxin. This protein enters the cells that line the intestine and modifies the subunit of a particular G proteinin such a way that it can no longer hydrolyze its bound GTP. The altered subunit thus remains in the active state indefinitely, continuously transmitting a signal to its target proteins. In intestinal cells, this causes a prolonged and excessive outflow of Cl– and water into the gut, resulting in cata- strophic diarrhea and dehydration. The condition often leads to death unless urgent steps are taken to replace the lost water and ions

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24
Q

G-protein subunits can be … or … in the plasma membrane

A

G-protein subunits can be ENZYMES or ION CHANNELS in the plasma membrane

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25
Q

There are about ? types of mammalian G proteins

A

20

26
Q

In heart muscle cells, how does G-protein signalling activation work? All players involved… draw!

A

Activation - ligand binds to GPCR -> activates G-protein (Gi) (GDP -> GTP) -> alpha subunit dissociates from beta/gamma subunit which moves to and causes opening of K+ channel -> K+ leaves cell -> cardiac cell decreases excitability.
Inactivation - alpha subunit -> hydrolysis (GTP -> GDP) -> Gi protein back to inactive state -> K+ channel closes

27
Q

The two most frequent target enzymes for G proteins are…

A

adenylyl cyclase -> cAMP

phospholipase C

28
Q

What are “first messengers”? What are “second messengers”?

A

“first messengers” - extracellular signals

“second messengers” - small intracellular signaling molecules part of ‘amplification’ (aka. small messengers)

29
Q

G-proteins activate membrane-bound enzymes involve what pathway? players…

A

alpha subunit activates the membrane-bound enzymes -> many small messenger (2nd messenger) molecules -> amplified signal -> specific signaling proteins

30
Q

What is adenylyl cyclase? Why is it important?

A

membrane-bound enzyme

activation of adenylyl cyclase converts ATP -> cAMP

31
Q

How does ATP -> cAMP -> AMP (in detail)… diagram is helpful figure 16.21 (slide 45)

A

activation of adenylyl cyclase converts ATP -> cAMP via removal of 2 phosphate groups and joins “free” end of remaining phosphate group to sugar part of ATP molecule then cAMP phosphodiesterase breaks this 2nd bond -> AMP

32
Q

What is the main function & main target of cAMP?

A

2nd messenger function & main target is cyclic- AMP–dependent protein kinase (PKA)

33
Q

cAMP properties…

A
  • small, water-soluble
  • can diffuse rapidly all over the cell
  • removed rapidly by the phosphodiesterase
  • concentrations can alter quickly and regionally
34
Q

Examples of cell responses mediated by cAMP…? target tissue? response?

A
  • Adr -> heart -> ++HR & contraction force
  • Adr -> skeletal muscle -> glycogen breakdown
  • ACTH -> adrenal gland -> cortisol secretion
35
Q

cAMP is involved in many signalling processes. Describe, in detail, with example, one of these signalling processes. good to draw! Its a tough mo fo!

A

Glycogen breakdown in skeletal muscle…
Adr activates GPCR -> activates G protein (Gs) -> alpha subunit -> adenylyl cyclase -> ATP->cAMP -> activates PKA -> activates phosphorylase kinase -> activates glycogen phosphorylase -> glycogen breakdown

36
Q

How does cAMP activate genes?

A

Adr activates GPCR -> activates G protein (Gs) -> alpha subunit -> adenylyl cyclase -> ATP->cAMP -> activates PKA -> active PKA -> nucleus -> phosphorylate & activate transcription factor (CREB) -> activates transcription (cell type specific)

37
Q

GPCRs activate Phospholipase C also. How? All players…draw - figure 16.25 (slide 51)

A

Ach -> GCPR -> alpha subunit G-protein -> phospholipase C -> inositol phospholipid -> IP3 & DAG -> IP3 -> ER -> Ca+ channel -> +++Ca+ in cytosol DAG & +++Ca+ -> activate PKC -> phosphorylates its own set of intracellular proteins, further propagating the signal (eg. smooth muscle contraction)

38
Q

What are some of the Ca2+ signal triggers?

A

sperm fertilising an egg -> +++Ca+ -> start development

signal from a nerve (skeletal muscle cells) -> +++Ca+ -> muscle contraction

39
Q

Concentration of [CA2+] in cytosol in normal conditions?

A

low - due to Ca2+ pumps out of cytosol -> ER or out of cell

40
Q

Most widespread and common Ca2+-responsive protein? what does it affect?

A

calmodulin - when bound to Ca2+ affects other proteins like CaM-kinase

41
Q

Fastest GPCR response?

A

response of eye to bright light (20msec)

42
Q

Serine/threonine kinases include…?

A

PKA
PKC
CaM-kinases

43
Q

What is RTK?

A

receptor tyrosine kinase

44
Q

Re. enzyme-coupled receptors, the catalytic domain can take 2 forms. what are they? slide 59

A

can be part of the receptor protein

or it can be a protein that is associated with the receptor

45
Q

How does the enzyme-coupled RTK pathway work? figure 16.30 (slide 60)…

A

signal molecule -> two receptor RTK molecule -> come together (dimerise) -> stimulates kinase domains -> phosphorylation of several tyrosines -> activates RTK -> draws in signalling proteins (6 of them) bound to the phosphorylated tyrosines -> signal relayed

46
Q

Definition of a “standard unit” of enzyme activity?

A

amount of an enzyme that will catalyse the transformation of 1 micromole of substrate per minute under standard conditions of temperature, optimal pH, and optimal substrate concentration

47
Q

as [substrate] decreases, enzyme activity …?

A

decreases

48
Q

As reaction volume increases, enzyme activity

A

decreases

49
Q

How tyrosine kinases activate signal pathways?

A

Ligand binding often dimerises RTK -> increase relative [ ] to each other & to the membrane -> cross phosphorylate each other -> accelerating their reactions

50
Q

Receptor tyrosine kinases often activate which molecule?

A

Ras - small GTP-binding protein (fig 16.31)

51
Q

How tyrosine kinases activate signal pathways thru Ras & MAP kinase?

A

signal molecule -> two receptor RTK molecule -> come together (dimerise) -> stimulates kinase domains -> phosphorylation of several tyrosines -> activates RTK -> draws in signalling proteins (6 of them) bound to the phosphorylated tyrosines -> signal relayed —-> Ras-activating protein recruited (colocalisation) -> GDP-Ras -> GTP-Ras (active) -> signal propagation -> activated MAP kinase kinase kinase -> activated MAP kinase kinase -> activated MAP kinase -> effector proteins -> survival, growth, mitogenic signals…

52
Q

Many of the extracellular signal proteins (eg IGF) that stimulate animal cells to survive, grow, and proliferate act through RTKs. Which crucially important enzyme is involved in this pathway? Describe… Figure 16-33

A

phosphoinositide 3-kinase (PI 3-kinase)
IGF -> RTK (activated) -> PI 3-kinase (activated) -> phosphorylated inositol phospholipid -> kinase Akt (activated) -> signal relayed onward

53
Q

What is the role of Akt kinase? How does it fit into the PI 3-kinase pathway?

A

phosphorylates & inactivates Bad (cell-death promoter) -> Bcl2 released -> inhibits apoptosis

54
Q

The PI3K/AKT pathway also stimulates cell growth via which molecule?

A

Target of Rapamycin (Tor)

55
Q

HOW WE KNOW: UNTANGLING CELL SIGNALING PATHWAYS…what are some techniques used to discern signalling pathways

A

stimulated phosphorylation - either breaking open cells to observe or radioactive ATP -> gel or x-ray film
co-immunoprecipitation - use of Ab bind to proteins & other proteins -> sink to bottom of test tube (IDs proteins. To ID specific parts of the protein that bind -> recombinant DNA technology -> mutant proteins -> which phosphorylated tyrosines attract which signalling proteins
Constantly active or inactive protein/gene - via recombinant DNA
Screening animals - mutagen to ID signalling pathway not functioning properly. Help determine order of sig. pathway

56
Q

What is important about the JAK/STAT pathway? describe it. Figure 16-39… eg?

A

eg. prolactin -> cytokine receptor (bound to JAK 1 & 2) -> receptors dimerise -> JAK kinases cross-phosphorylate each other & receptor proteins -> STAT5 binds to receptor & are also phosphorylate by JAKs -> fuck off to nucleus -> transcription of genes that encode milk proteins

57
Q

How does the RTK activation of Ras pathway go?

A

signal molecule -> two receptor RTK molecule -> come together (dimerise) -> stimulates kinase domains -> phosphorylation of several tyrosines -> activates RTK -> draws in signalling proteins (6 of them) (one is Grb2) bound to the phosphorylated tyrosines -> Ras-activating protein recruited (GEF, called Sos - colocalisation) -> GDP-Ras -> GTP-Ras (active) -> signal propagation

58
Q

An even more direct signaling pathway is used than JAK/STAT. What is it? How does it work?

A

Notch receptor which is a transcription regulator. How?
Here’s how…
Binding of delta protein (attached to neighbouring cell) to Notch -> Notch receptor cleaved -> remaining tail of Notch fucks off to nucleus to activate Notch-responsive genes

59
Q

T or F - Multicellularity and Cell Communication Evolved Independently in Plants and Animals

A

true

60
Q

Define, a fucking protein kinase!

A

kinase enzyme that modifies other proteins by chemically adding phosphate groups to them (phosphorylation)

61
Q

Signalling pathways can be highly interconnected. Draw full flow diagram illustrating all of these pathways…

A

Figure 16-42 or slide 86

62
Q

Draw the integrating pathways of 2 different scenarios A & B.

A

Figure 16-43 or slide 87