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Foundations of health and disease > cell signalling > Flashcards

cell signalling Flashcards

1
Q

why do cells communicate

A
  • Respond to immediate environment – including danger signals
  • Respond to central commands
  • Respond to local commands
  • Respond accordingly
  • Coordinate cellular responses
  • Integrate signals from multiple sources
  • Induce / decrease growth (division) if the need arises
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2
Q

what are the 3 types of intercellular signalling

A

chemical
physical
gaseous

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3
Q

what is intercellular signalling

A

between cells

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4
Q

what are signalling molecules that bind and activate receptors

A

agnosits/ligands

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5
Q

what are signaling molecules that bind to and inactivate receptors

A

antagonists/blockers

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6
Q

what are transmembrane/ cell surface receptors

A

Respond to signals on the outside of the cell by interacting with molecules on the inside

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7
Q

what are the types of transmembrane / cell surface receptors

A

G protien coupled receptors (GPCRs)
ion channel linked receptors
enzyme receptors

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8
Q

why are transmembrane receptors important

A
  • Most signalling molecules are too large or too hydrophilic to cross the membrane
  • Ligand binding changes the activities of the intracellular domains of the receptor, which initiates the response
  • The signalling molecule itself doesn’t need to enter the cell
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9
Q

what kind of receptor is this

A

cytoplasmic and nucelar

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10
Q

what are cytoplasmic and nuclear receptors

A
  • Small molecules and hydrophobic molecules can cross the cell membrane
  • Bind directly to receptors in the cytosol or the nucleus
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11
Q

what kind of receptor is this

A

transmembrane

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12
Q

what determines how different cells can respond differently to the same signal

A

The sets of receptors the cell has

The intracellular machinery

This explains why drugs sometimes have additional unwanted effects

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13
Q

what are the 5 modes of intercellular signalling

A

endocrine
paracrine
neuronal
autocrine
juxtacrine

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14
Q

which types of intercellular signalling is long range

A

endorcine

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15
Q

which types of intercellular signalling are short range

A

paracrine
neuronal
autocrine
juxtacrine

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16
Q

what is a hormone

A

a compound produced by an endocrine gland and released into the bloodstream where it acts on target cells at a distance location

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17
Q

what is endocrine signalling

A
  • low chemical communication
  • Hormones are released and circulate in the blood, coming into contact with most cells within the body (hence long distance)
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18
Q

why can only a limited number of cells respond to a hormone?

A

must express the correct receptor to interpret the signal

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19
Q

what do hormones do during intercellular signalling

A

Hormones regulate cell reactions by affecting gene expression

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20
Q

what is paracrine signalling

A
  • Signalling molecules are released from one cell and diffuse locally to neighbouring cells
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21
Q

what are kinds of paracrine signals

A

proteins
amino acid derivatives
dissolved gas

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22
Q

what kind of signalling is this?

A

paracrine

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23
Q

what is neuronal/ neurocrine signalling

A
  • Deriving from a nerve
  • Neurotransmitters travel only across the synaptic gap to the adjacent target cell only (e.g. nerve cell, muscle cell)
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24
Q

what is an example of neuronal signalling

A

noradrenaline, secreted form sympathetic nerve terminal to act at adrenoceptors to contract blood vessels

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25
Q

what kind of signaling is this?

A

neuronal

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26
Q

what is autocrine signalling

A

Cells secrete signalling molecules that bind their own receptors to generate a change in their own behaviour

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27
Q

what is an example of autocrine signaling

A
  • Example: cytokine interleukin-1 in monocytes
    • Interleukin-1 is produced in response to external stimuli
    • Binds to cell-surface receptors on the same cell that produced it
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28
Q

how does autocrine signalling maintain homeostasis

A

Sometimes the binding to their own receptors can lead to an increase (positive feedback) or decrease (negative feedback) the molecule production

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29
Q

what is juxtacrine signalling

A
  • Contact-dependent signalling: immediate neighbours signal to eachother via membrane bound molecules
  • Does not require the release of a signalling molecule
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30
Q

what are examples of juxtacrine signalling

A

contact dependant ligang binding
communication junctions- gap junctions

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31
Q

what is contact-dependant receptor-ligand binding

A

type of juxtacrine signalling
direct cell to cell communication or interactions with the extracellular matrix (ECM)

32
Q

what is an example of contact-dependant receptor-ligand binding

A

Antigen presentation requires contact between the two cell types

33
Q

what are communication junctions

A

tpye of juxtacrine signaling
Provide neighbouring cells with a direct communication link that can be opened or closed in response to the cell environment similar to an ion channel

34
Q

what are the features of communication junctions?

A
  • Channels form between cells allowing diffusion of small molecules such as ions, nucleotides and sugars
  • Narrow pore spanned by pore-forming proteins called connexins
  • Provide rapid metabolic and electrical coupling
35
Q

what is an example of a gap junction

A
  • Gap junctions between heart muscle cells allow waves of electrical excitation to pass quickly through the tissue
  • Gap junctions appear in the myometrium of the uterus towards to the end of pregnancy, where they help coordinate uterine contractions during childbirth
36
Q

what are 2 examples of endocrine signalling

A

insulin
stress response

37
Q

what is the insulin endocrine signalling response

A

secreted from pancreas
released into the bloodstream
act at insulin receptors to promote glucose

38
Q

what are the signalling errors of insulin

A

Type 1 diabetes- no insulin made
type 2 diabetes- absent or decreased response to insulin by target cells

39
Q

what is the endocrine signalling response for stress response

A

cortisol binds to the glucocorticoid receptor (GR)- can both activate and suppress gene expression
produce both metabolic and anti-inflammatory effects

40
Q

what are the clinical uses of corticosteroids

A

synthetic compounds that activate GR
autoimmunity, allergic reactions, asthma

41
Q

what are examples of paracrine signalling

A

nitric oxide

42
Q

what is the features of nitric oxide in paracrine signalling

A

produced by nitric oxide synthase (NOS) and diffuses into nearby smooth muscle cells and activates its target enzyme
short half-life

43
Q

what does NO cause

A

causes vasorelaxation, platelet aggregation and immune responses
reduced levels in most cardiovascular disorders

44
Q

what does receptor activation lead to

A

intracellular signalling cascades and second messenger systems

45
Q

how are signals created by messengers turned off

A

Chemical signals are enzymatically degraded

G proteins become inactivated by GTPases

46
Q

what are the 3 stages of intracell communication

A

reception
transduction
response

47
Q

what is reception in intracell communication

A

a chemical message binds to a protein on the cell surface

48
Q

what is transduction in intraacell communication

A

the binding of the single molecule alters the receptor
this starts a cascade of reactions

49
Q

what is response in intracell communication

A

the transduction pathway triggers a response
this can be: turning on a gene, activating an enzyme, rearranging the cytoskeleton

50
Q

how are signalling molecules controlled

A

By post translational modification, e.g. phosphorylation
By regulating whether a G protein has bound GDP or GTP
By provision of activators such as Ca2+ and cAMP

51
Q

what is a kinase

A

Kinase is an enzyme that phosphorylates proteins

52
Q

what do kinases do

A

add a phosphate group

53
Q

what is phosphatase

A

enzyme that dephosphorylates proteins

54
Q

what are examples of serine/threonine kinases

A

CAMK- ca+
PKA
PKC
MAPK

55
Q

what are 2 types of tyrosine kinases

A

non reeptor and receptor tyrosine kinases

56
Q

what are integral membrane proteins

A

Integral membrane proteins transmit the signal into the cell; these receptors span the membrane.

57
Q

what molecules cant cross the lipid bilayer

A

proteins
peptides
charged molecules

58
Q

how do ligands interact with receptors

A

Ligands may interact directly with the receptors or by binding to co-receptors or accessory molecules on the cell surface

59
Q

what happens when transmembrane receptors are activated

A

Receptor activation causes a conformational change in the tertiary or quaternary structure that allows initiation of signalling

60
Q

how are ion channels structured

A

5 transmembrane subunits come together to form a channel

61
Q

what do ion channels transport

A

K+
Na+
Ca+
Cl-

62
Q

what are the 2 responses ion channels open to

A

Changes in the transmembrane potential: Voltage-gated ion channels
A chemical binds: Ligand-gated ion channels / ionotropic receptors

63
Q

what are features of ion channels

A

FAST regulated opening/closing mechanism
Once activated, allow ions to move through - changes the electrical properties of the cell

64
Q

what are Ligand-gated ion channels / Ionotropic receptors

A

Transmembrane proteins consisting of a receptor part and a channel which traverses the membrane
Open in response to binding of a ligand
Once activated will still allow ions to go through (Na+, K+, Ca2+, Cl-) however they are classified according with the ligand binding to them

65
Q

what are examples of ligand gated ion channels

A

nicotinic- acetylcholine receptor
GABA receptor
Glycine receptor
5-HT3 receptor

66
Q

what are features of G-Protein coupled receptors (GPCRs)

A

Largest group of receptors
A single long polypeptide chain folded 7 times into a globular shape with portions inside and outside of the cell
Interact with G proteins in the plasma membrane that have 3 subunits; α, b and y

67
Q

what are the 3 types of Ga proteins

A

Gai/o
Gas
Gaq

68
Q

why are there 3 different types of Ga proteins

A

coupled to different intracellular signalling pathways

69
Q

what are second messenger systems

A

Second messenger systems - concentration changes in response to receptor activation by agonist

70
Q

what is the Gai protein signalling pathway

A

GPCR
Gai protein
adenylyl cyclase
cAMP
PKA

71
Q

what is the Gaq protein signalling pathway

A

GPCR
Gaq protein
phospholaise c (PLC)
Diacylglycerol (DAG) -> protein kinase C (PKC)
IP3 -> Ca2+ released from the ER -> PKC

72
Q

what is the by subunit signalling pathway

A

GPCR
by subunit
K+ channel
K+ move out the cell

73
Q

what are features of enzyme linked receptors

A

These receptors usually have a single membrane spanning domain
The cytoplasmic enzymes that induce signalling are normally protein tyrosine kinases
Extracellular ligand binding domain, a single transmembrane helix, a cytoplasmic region containing the protein tyrosine kinase activity

74
Q

what are features of receptor tyrosine kinases

A

Ligand binding activates enzyme activity within the cytoplasmic domain
The response usually requires receptor dimerisation
Tyrosine residues in the intracellular domains are auto-phosphorylated in response to the signal
Typically, responses are slow

75
Q

what are features of cytoplasmic/nuclear signalling

A

For signals that can cross the cell membrane
Alter gene transcription (and hence protein levels) directly

Foundations of health and disease (21 decks)

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