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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
Agonists
ligands that when bound to the receptor, change the receptor’s activity to produce a response
26
Antagonists
ligands that when bound to the receptor, do not produce a response
27
a single receptor may bind _____ different ligands, and a single ligand may bind to ____ different receptors
several x2
28
_____ is a neurotransmitter that is released from the pre-synaptic terminals of neurons
Acetylcholine (ACh)
29
In skeletal muscle, the ACh receptors are ______
ion-channel receptors aka nicotinic receptors
30
ACh receptors: can also bind two naturally occurring toxins:
α-bungarotoxin (Taiwanese Krait, elapid snake) & tubocurare (South American plant)
31
α-bungarotoxin & tubocurare bind the ACh receptor with _____ than ACh
higher affinity
32
α-bungarotoxin & tubocurare bind the ACh receptor; how do they work
They bind to the receptor, blocking the binding of ACh, resulting in paralysis of the diaphragm & subsequent death
33
Transmembrane receptors
cell membrane receptors that bind ligand outside the cell
34
Transmembrane receptors: most ligands are
hydrophilic
35
majority of receptors are
transmembrane receptors
36
3 types of transmembrane receptors
* Ion channel-linked receptors * Enzyme-linked receptors * G protein-coupled receptors
37
Ion Channel-linked Receptors
* 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
Ion Channel-linked Receptors: Transmembrane (integral) proteins have a _____ central canal
hydrophilic central canal (pore)
39
ion channel-linked receptors; how are transmembrane (integral) proteins open and closed
* 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
Enzyme-linked Receptors; type of transmembrane receptors
Either enzymes themselves or are directly associated with the enzymes they activate
41
Enzyme-linked Receptors; enzymatic portion is usually
intracellular
42
enzyme-linked receptors: Majority are
protein kinases, or are associated with protein kinases
43
Enzyme-linked Receptors Protein kinase receptors: * A cell’s response to a signal often involves
activating or inactivating proteins
44
______ is a common way to change the activity of a protein
Phosphorylation (adding a phosphate group)
45
Kinases
are enzymes that transfer phosphate groups from ATP to another protein
46
* Receptor Tyrosine Kinases (RTKs) type of enzyme-linked receptors
RTKs transfer phosphate groups to tyrosine residues (amino acids)
47
When the signalling molecules bind to two adjacent recetor tyrosine kinases (RTKs) ,
they bond together (dimerise)
48
when Receptors tyrosine kinases are bond together (dimerise) what happens next type of enzyme-linked receptor
* 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
enzyme-linked receptors kinase cascase
* A series of protein kinases that phosphorylate each other in succession * Amplifies the signal
50
melanoma: >50% carry mutations in kinases such as BRAF -->
--> constitutive activation --> uncontrolled cell proliferation
51
G Protein-coupled Receptors
* Transmembrane (integral) proteins * Also known as Seven Transmembrane Receptors (7TM receptors) * Coupled to a G protein
52
ligands of G protein-coupled receptors include
odours, pheromones, hormones, neurotransmitters, light E, lipids & sugars
53
G proteins
Specialised proteins that bind to nucleotides Guanosine Triphosphate (GTP) & Guanosine Diphosphate (GDP)
54
G proteins have __ subunits
3; α, β, γ
55
G proteins: alpha subunit bind
GTP or GDP, depending on whether the protein is active or inactive
56
G proteins; in the absence of a signal
GDP binds & the entire G protein-GDP complex binds to a nearby GPCR
57
When a signalling molecule binds to the G protein-coupled receptor
the GPCR changes conformation & activates the G protein, GTP replaces GDP Numerous second messengers produced
58
intracellular receptors; Many small signalling molecules are _____
hydrophobic
59
intracellular receptors Transported in
blood & extravascular fluids bound to carrier proteins
60
how do intracellular receptors enter cell
But are lipophilic so dissociate from carrier protein to enter cell
61
Steroid hormones, thyroid hormones, vitamin D3, retinoic acid are examples of
intracellular receptors
62
steroid hormone signalling steps (intracellular receptors)
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. 4. The steroid-receptor complex is called a transcription factor and by interacting with the DNA alters the expression of specific genes.
63
signal transduction After the ligand binds to the receptor, the receptor interacts with other ______
intracellular signalling molecules
64
second messengers
* Small molecules & ions that relay signals received by cell-surface receptors * Because they are small, they diffuse rapidly
65
second messengers are small so they
diffuse rapidly
66
second messengers examples
* Cyclic nucleotides: cAMP, cGMP * Ions: Ca2+ * Phospholipid-derived molecules: inositol triphosphate * Gases: nitric oxide
67
cyclic adenosine monophosphate (cAMP) is synthesized by
adenyl cyclase enzymes from ATP
68
describe adrenaline signalling in skeletal muscle
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
Caffeine enhances the action of cAMP by
inhibiting the enzyme phosphodiesterase (PDE) that degrades cAMP
70
Each molecule of adrenaline that arrives at the cell membrane results in _____ molecules of glucose in the blood:
10,000
71
Ca2+ concentration inside cells much _____ than outside
lower
72
Many signalling molecules induce responses in cells via signal transduction pathways that ____ cytoplasmic levels of Ca2+
increase
73
_____ functions as a second messenger in G protein & tyrosine kinase pathways
Ca2+
74
what triggers release of Ca2+ from ER
signal transduction --> cell response
75
Phosphoinositol Signalling Pathway
* 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
Phosphoinositol Signalling Pathway steps summary (6 steps)
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
_____ inhibition of the Phosphoinositol Signalling Pathway to treat bipolar disorder
lithium
78
nitric oxide
free radical that diffuses across cell membranes
79
nictric oxide is both
* Both hydrophilic & lipophilic * Acts in a paracrine or autocrine manner
80
nitric oxide Plays an important role in many physiological processes including
neuronal signalling, immune responses, inflammatory responses, modulation of ion channels, phagocytosis, vasodilation…
81
NO signalling in vasodilation
* 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
exosomes
* Membrane-bound extracellular vesicles * Generated by all cells * Contained within multivesicular bodies
83
exosomes contain
* Contain proteins, lipids, metabolites, DNA, RNA
84
exosomes are taken up by cells via
endocytosis, where they affect function
85
exosomes; what do they do, what are they involved in
* 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
exosomes ar engineered to deliver
therapeutic payloads, including chemotherapeutic agents, immune modulators…
87
exosomes have potential to aid in
disease diagnosis
88
what fluids are exosomes present in
Present in all biological fluids: makes them easy to sample in liquid biopsies

AGRC1041 (20 decks)

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