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AGRC1041 > cell signalling 1, 2, 3 > Flashcards

cell signalling 1, 2, 3 Flashcards

1
Q

if cells are deprived from cell signaling they will undergo

A

apoptosis

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2
Q

cell signals conveyed by ______ signalling molecules

A

extra-cellular

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3
Q

3 stages of cell signaling

A

1) reception: Signalling molecule binds to cellular receptor, typically on the cell surface

2) transduction: Binding leads to a change in the receptor that triggers a series of actions along a signal transduction pathway

3) response: The transduced signal triggers a specific cellular response

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4
Q

Ligands

A

signalling molecules; Growth factors, hormones, cytokines & chemical mediators (eg toxins)

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5
Q

receptors

A

Each cell type displays a set of
receptors that enable it to respond to the ligands (signalling molecules) produced by other cells

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6
Q

Most signalling molecules are _____ & too large to pass through the plasma membrane so they bind to transmembrane proteins called

A

water-soluble
Surface receptors

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7
Q

some signaling molecules are lipid soluble , what do they bind to

A

pass through plasma membrane and bind to cytoplasmic or nuclear receptors

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8
Q

Signalling molecules can trigger a change in the metabolism of a cell, give an ex

A

eg insulin signalling through the insulin receptor

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9
Q

Signalling molecules can trigger a change in the electrical potential across the membrane of a cell, give an ex

A

eg neurotransmitter signalling in neurons

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10
Q

Signalling molecules can trigger a change in gene expression (transcription) within the nucleus, give an ex

A

eg adrenaline binding to an Adrenergic Receptor

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11
Q

types of signalling molecules

A
  • Hormones
  • Growth factors: Proteins that stimulate cell growth, differentiation
  • Cytokines: Small proteins/peptides
  • Chemokines: A type of cytokine
  • Neurotransmitters
  • Neurohormones
  • Infectious agents
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12
Q

Endocrine Signalling

A
  • Ligands: hormones
  • Long-distance signalling via the blood
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13
Q

Paracrine Signalling

A
  • Ligands: growth factors, cytokines, chemokines & hormones
  • Neurotransmitters – special form of paracrine signalling
  • Acts locally or over short distances, via the blood or interstitial fluid
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14
Q

Autocrine Signalling

A
  • Ligands: cytokines & chemokines
  • Autostimulation; Signalling molecules bind to receptors on the same cell
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15
Q

Juxtacrine (Contact-dependent) Signalling

A
  • Ligands: proteins attached to plasma membrane of cell
  • Receptors on adjacent cell
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16
Q

After the ligand binds to the receptor, the receptor interacts with other

A

intracellular signalling molecules

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17
Q

some cellular responses to cell signalling

A

changes in:
* Metabolism
* Growth
* Differentiation
* Gene expression
* Secretion
* Structure
(cytoskeleton)

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18
Q

receptors have a high affinity for their

A

ligands

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19
Q

receptors have specificity for their ligands
Specificity depends on

A

binding affinity between the ligand & the binding site on the receptor

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20
Q

The affinity between receptors & their ligands is described by the

A

equilibrium dissociation constant KD

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21
Q

KD quantifies

A

the equilibrium between a ligand being free in solution or bound to its receptor –> Corresponds to the affinity of a ligand for the binding site on a receptor

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22
Q

KD is the concentration of ligand required for

A

50% of the surface receptors to be bound by ligand

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23
Q

The higher the KD, the _____ the binding & the lower the affinity.

A

weaker

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24
Q

Ligands are classified as either receptor ____ or ____, depending on the outcome of ligand-receptor binding

A

agonists or antagonists

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25
Q

Agonists

A

ligands that when bound to the
receptor, change the receptor’s activity to produce a response

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26
Q

Antagonists

A

ligands that when bound to the receptor, do not produce a response

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27
Q

a single receptor may bind
_____ different ligands, and a single ligand may bind to ____ different receptors

A

several x2

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28
Q

_____ is a neurotransmitter
that is released from the pre-synaptic terminals of neurons

A

Acetylcholine (ACh)

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29
Q

In skeletal muscle, the ACh receptors are ______

A

ion-channel receptors aka nicotinic receptors

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30
Q

ACh receptors: can also bind two naturally occurring toxins:

A

α-bungarotoxin (Taiwanese
Krait, elapid snake) & tubocurare (South American plant)

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31
Q

α-bungarotoxin & tubocurare bind the ACh receptor with _____ than ACh

A

higher affinity

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32
Q

α-bungarotoxin & tubocurare bind the ACh receptor; how do they work

A

They bind to the receptor, blocking the binding of ACh, resulting in paralysis of the diaphragm & subsequent death

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33
Q

Transmembrane receptors

A

cell membrane receptors
that bind ligand outside the cell

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34
Q

Transmembrane receptors: most ligands are

A

hydrophilic

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35
Q

majority of receptors are

A

transmembrane receptors

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36
Q

3 types of transmembrane receptors

A
  • Ion channel-linked receptors
  • Enzyme-linked receptors
  • G protein-coupled receptors
37
Q

Ion Channel-linked Receptors

A
  • type of transmembrane receptors
  • Cation & anion channels
  • Involved in rapid signalling events
  • Generally found in electrically excitable cells (eg neurons)
  • Also called ligand-gated ion channels
38
Q

Ion Channel-linked Receptors: Transmembrane (integral) proteins have a _____ central canal

A

hydrophilic central canal (pore)

39
Q

ion channel-linked receptors; how are transmembrane (integral) proteins open and closed

A
  • Opened and closed by gates
  • Conformational change of protein opens or closes the pore via gates
  • Opening & closing of gates controlled by binding of ligand
40
Q

Enzyme-linked Receptors;
type of transmembrane receptors

A

Either enzymes themselves or are
directly associated with the enzymes they activate

41
Q

Enzyme-linked Receptors; enzymatic portion is usually

A

intracellular

42
Q

enzyme-linked receptors: Majority are

A

protein kinases, or are associated with protein kinases

43
Q

Enzyme-linked Receptors

Protein kinase receptors:
* A cell’s response to a signal often involves

A

activating or inactivating proteins

44
Q

______ is a common way to change the activity of a protein

A

Phosphorylation (adding a phosphate group)

45
Q

Kinases

A

are enzymes that transfer phosphate groups from ATP to another protein

46
Q
  • Receptor Tyrosine Kinases (RTKs)

type of enzyme-linked receptors

A

RTKs transfer phosphate groups to tyrosine residues (amino acids)

47
Q

When the signalling molecules bind to two
adjacent recetor tyrosine kinases (RTKs) ,

A

they bond together (dimerise)

48
Q

when Receptors tyrosine kinases are bond together (dimerise) what happens next

type of enzyme-linked receptor

A
  • Phosphates are then added to the tyrosine
    residues on the intracellular domain of the
    receptors (phosphorylation)
  • The phosphorylated residues then transmit the
    signal to the next messenger in the cytoplasm
49
Q

enzyme-linked receptors

kinase cascase

A
  • A series of protein kinases that phosphorylate each other in succession
  • Amplifies the signal
50
Q

melanoma: >50% carry mutations in kinases such as BRAF –>

A

–> constitutive activation –> uncontrolled cell proliferation

51
Q

G Protein-coupled Receptors

A
  • Transmembrane (integral) proteins
  • Also known as Seven Transmembrane
    Receptors (7TM receptors)
  • Coupled to a G protein
52
Q

ligands of G protein-coupled receptors include

A

odours, pheromones,
hormones, neurotransmitters, light E,
lipids & sugars

53
Q

G proteins

A

Specialised proteins that bind to nucleotides Guanosine Triphosphate (GTP) & Guanosine Diphosphate (GDP)

54
Q

G proteins have __ subunits

A

3;
α, β, γ

55
Q

G proteins: alpha subunit bind

A

GTP or GDP, depending on
whether the protein is active or inactive

56
Q

G proteins; in the absence of a signal

A

GDP binds & the entire G protein-GDP complex binds to a nearby GPCR

57
Q

When a signalling molecule binds to the G protein-coupled receptor

A

the GPCR changes conformation & activates the G protein, GTP replaces GDP

Numerous second messengers produced

58
Q

intracellular receptors; Many small signalling molecules are _____

A

hydrophobic

59
Q

intracellular receptors Transported in

A

blood & extravascular fluids
bound to carrier proteins

60
Q

how do intracellular receptors enter cell

A

But are lipophilic so dissociate from carrier protein to enter cell

61
Q

Steroid hormones, thyroid hormones, vitamin D3, retinoic acid are examples of

A

intracellular receptors

62
Q

steroid hormone signalling steps
(intracellular receptors)

A
  1. Transported in the blood bound to carrier proteins –> surface of their target cell.
  2. The steroid drops off the carrier and the free steroid enters the cell.
    3a. Some steroids bind to a cytoplasmic receptor which conveys them into the nucleus.
    3b. Others do not bind to a receptor until they enter the nucleus.
  3. The steroid-receptor complex is called a transcription factor and by interacting with the DNA alters the expression of specific genes.
63
Q

signal transduction
After the ligand binds to the receptor, the receptor interacts with other ______

A

intracellular signalling molecules

64
Q

second messengers

A
  • Small molecules & ions that relay signals received by cell-surface receptors
  • Because they are small, they diffuse rapidly
65
Q

second messengers are small so they

A

diffuse rapidly

66
Q

second messengers examples

A
  • Cyclic nucleotides: cAMP, cGMP
  • Ions: Ca2+
  • Phospholipid-derived molecules: inositol triphosphate
  • Gases: nitric oxide
67
Q

cyclic adenosine monophosphate (cAMP) is synthesized by

A

adenyl cyclase enzymes from ATP

68
Q

describe adrenaline signalling in skeletal muscle

A

Adrenaline binds to GPCR β-adrenergic receptors –>
G protein activation stimulates cAMP synthesis by adenylyl cyclase –>
cAMP activates protein kinase A –>
activates phosphorylase kinase –>
activates glycogenphosphorylase –> glycogen breakdown –> glucose released into blood

69
Q

Caffeine enhances the action of cAMP by

A

inhibiting the enzyme phosphodiesterase (PDE) that degrades cAMP

70
Q

Each molecule of
adrenaline that arrives
at the cell membrane
results in _____ molecules of glucose in
the blood:

A

10,000

71
Q

Ca2+ concentration inside cells much _____ than outside

A

lower

72
Q

Many signalling molecules induce
responses in cells via signal transduction pathways that ____
cytoplasmic levels of Ca2+

A

increase

73
Q

_____ functions as a
second messenger in G
protein & tyrosine
kinase pathways

A

Ca2+

74
Q

what triggers release of Ca2+ from ER

A

signal transduction

–> cell response

75
Q

Phosphoinositol Signalling Pathway

A
  • Adrenaline binds to a GPCR –> GPCR changes
    conformation & activates the G protein, GTP replaces GDP
  • The activated α subunit activates phospholipase
    C –> hydrolyses phosphatidylinositol 4,5- bisphosphate (PIP2) –> results in the formation of second messengers diacylglycerol (DAG) and inositol-1,4,5-triphosphate (IP3)
  • IP3 binds to calcium pumps on ER –> Ca2+
    released into the cytoplasm –> Ca2+ binds to many proteins, activating a cascade of
    enzymatic pathways
76
Q

Phosphoinositol Signalling Pathway steps summary (6 steps)

A

1) ligand binding
2) G alpha and RTK activation
3) PLC activation and G alpha and RTK
4) PIP2 –> IP3 + DAG
5) IP3R binding Ca2+ release
6) IP3 phosphorylation by ITP3K

77
Q

_____ inhibition of the Phosphoinositol Signalling Pathway to treat bipolar disorder

A

lithium

78
Q

nitric oxide

A

free radical that
diffuses across cell membranes

79
Q

nictric oxide is both

A
  • Both hydrophilic & lipophilic
  • Acts in a paracrine or autocrine manner
80
Q

nitric oxide Plays an important role in many physiological processes including

A

neuronal signalling, immune responses, inflammatory responses, modulation
of ion channels, phagocytosis, vasodilation…

81
Q

NO signalling in vasodilation

A
  • ACh binds to the GPCR –> GPCR activates phospholipase C (PLC), which catalyses the
    production of IP3 –> IP3 acts on the IP3-
    gated Ca2+ channel in the ER –> release of
    Ca2+
  • Ca2+ binds to calmodulin (CaM) to form Ca2+-CaM complex –> reactivates NO synthase (eNOS) in endothelial cells –> NO produced –> NO diffuses into vascular smooth muscle
    cells…smooth muscle relaxation
82
Q

exosomes

A
  • Membrane-bound extracellular vesicles
  • Generated by all cells
  • Contained within multivesicular bodies
83
Q

exosomes contain

A
  • Contain proteins, lipids, metabolites, DNA, RNA
84
Q

exosomes are taken up by cells via

A

endocytosis, where they affect function

85
Q

exosomes; what do they do, what are they involved in

A
  • Associated with pathogenesis of cancer,
    inflammation, neurodegeneration…
  • Likely involved in cell-cell communication
  • Proteins, metabolites & nucleic acids delivered into recipient cells alter their biological response
  • Exosome-mediated responses can both
    promote & suppress disease progression
86
Q

exosomes ar engineered to deliver

A

therapeutic payloads,
including chemotherapeutic agents, immune modulators…

87
Q

exosomes have potential to aid in

A

disease diagnosis

88
Q

what fluids are exosomes present in

A

Present in all biological fluids: makes them easy to sample in liquid biopsies

AGRC1041 (20 decks)

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