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BIOSCI107 > Lecture 8: How Cells Communicate > Flashcards

Lecture 8: How Cells Communicate Flashcards

1
Q

Why do cells communicate (ceels need, they respond)

A

Cells need to be able to respond as a cell, and as part of a whole tissue

They respond to signals from other cells and from the environment

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2
Q

Why do cells communicate (these)

A

These signals are often chemical (but can also be light, taste, smell etc)

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3
Q

Secreted signals can be

A

long or local distance

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4
Q

Local signaling

A

Signals act on nearby target cells

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5
Q

Signals act on nearby target cells (growth, neurotransmitters)

A

growth factors such as fibroblast growth factor – FGF1 (paracrine)

Neurotransmitters such as acetylcholine – ACh (synaptic)

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6
Q

Signals act on nearby target cells (Can act)

A

Can act on the signaling cell (autocrine)

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7
Q

Long distance signaling

A

signals act from a distance

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8
Q

signals act from a distance (hormones)

A

hormones secretes from endocrine cells travel via circulatory ststem to act on target cells

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9
Q

signals act from a distance (hormones eg;)

A

insulin secreted from pancreatic beta cells enters blood stream & travels and is detected by various body cells.

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10
Q

Cell signaling : Three main steps

A

Reception, Transduction, Response

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11
Q

Cell signaling : Three main steps (during the transduction)

A

During the transduction pathway multiple proteins may be activated, typically via phosphorylation

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12
Q

Reception

A

Signalling protein (primary messenger) binds to a receptor protein

Results in shape and/or chemical state change in the receptor protein

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13
Q

Transduction (altered)

A

Altered receptor activates a another protein, eg G-protein/adenylyl cyclase

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14
Q

Transduction (The activation)

A

The activated protein (often an enzyme) may cause a relay of changes

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15
Q

Transduction (Relay molecule)

A

Relay molecules known as “second messengers”, eg. cAMP, IP3

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16
Q

Transduction (Multiple)

A

Multiple other proteins may be activated

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17
Q

Transduction (each activated)

A

Each activated protein causes a series of changes, this is often via
phosphorylation – known as a phosphorylation cascade

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18
Q

Reponse (all, this)

A

All of the activated proteins cause one or more functions to occur in the cell

This is where the cell actually does something

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19
Q

Receptors are

A

Specific

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20
Q

Receptors - the human body

A

The human body will simultaneously send out many different chemicals and molecules, all aimed at eliciting specific responses BUT only the target receptors will interact with that signal (ligand) and use it to activate signal transduction pathways

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21
Q

Where does this specifically come from?

A

3D molecular shape of the proteins involved
…..structure determines function…..

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22
Q

Receptor - exquisite control is possible (only certain)

A

Only certain cells at certain times will have particular receptors (ie. dynamic), meaning that while the signal might be widespread the transmission of the signal occurs only where it is needed.

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23
Q

Receptor location (receptors for water)

A

Receptors for water soluble molecules are membrane bound

eg. G Protein Coupled Receptor, Receptor Tyrosine Kinase, ligand-gated ion channel

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24
Q

Receptor location (receptors for)

A

lipid soluble molecules are not membrane bound

Can be located in the cytoplasm or inside the nucleus

eg. lipid soluble hormones such as testosterone, estrogen, progesterone, thyroid hormones bind to receptors within the cytoplasm and move to nucleus as a complex

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25
G-protein coupled receptors (GPCRs)
Transmembrane proteins GPCRs couple with G protein
26
Transmembrane proteins (pass, hundreds, many, diverse)
pass PM 7 times Hundreds of different GPCRs exist Many different ligands Diverse functions: eg. development, sensory reception (vision, taste, smell)
27
GPCRs couple with G protein
G proteins are molecular switches which are either on or off depending on whether GDP or GTP is bound (GTP: guanosine triphosphate, similar to ATP)
28
GPCRs
29
Ligand gated ion channels/receptors (these channel)
These channel receptors contain a “gate” channel opens /closes as the receptor changes shape
30
Ligand gated ion channels/receptors (ions)
ions can pass through channel (eg. Na+, K+, Ca2+, and/or Cl−)
31
Ligand gated ion channels/receptors (binding of ligand)
Binding of ligand (eg neurotransmitter) at specific site on receptor elicits change in shape
32
Receptor
a molecule/protein which responds to a specific ligand
33
Ligand
a signalling molecule that binds specifically to another protein
34
Ion channel
membrane protein through which specific ions can travel
35
Ion channel receptor
membrane protein through which specific ions can travel, in response to ligand binding (also known as ionotropic receptors)
36
At rest
ligand is unbound and gate is closed
37
Upon ligand binging
gate opens, specific ions can flow into cell.
38
Following ligand dissociation
gate closes, back to resting.
39
Signal Transduction Pathways
Signals relayed from receptors to target molecules via a ‘cascade’ of molecular interactions
40
A typical phosphorylation cascade:
Protein kinases Phosphatases
41
Protein kinases (are enzymes)
are enzymes that transfer a phosphate group from ATP to another (specific) protein (kinases phosphorylate). Typically, this activates the protein
42
Protein kinases (series)
Series of protein kinases each adding a phosphate to the next kinase.
43
Phosphate
are enzymes that dephosphorylate (remove the phosphate) rendering the protein inactive, but recyclable
44
Single transduction pathways
Typically, it is serine or threonine residues that are phosphorylated. This means that mutations affecting these residues could be detrimental.
45
Use of a second messenger - cAMP
Sometimes another small molecule is included in the cascade, these are second messengers. eg. cAMP and calcium ions
46
cAMP acts
cAMP acts as a second messenger and activates downstream proteins, for example, PKA which phosphorylates other proteins
47
cAMP - the activated, activated
The activated enzyme is adenylyl cyclase Activated adenylyl cyclase converts ATP to cAMP
48
Calcium is a widely used second messenger
Low [Ca 2+ ] inside cell (typically ~100nm) Very high [Ca 2+ ] outside the cell (more than 1000-fold higher)
49
Maintenance of concentration
via calciumpumps is important -out of cell -into ER -into mitochondria
50
Ca 2+ and IP3 in GPCR signalling (here)
Here, the activated protein is phospholipase C which then cleaves PIP2 (a phospholipid) into DAG and IP3
51
Ca 2+ and IP3 in GPCR signalling (IP3)
IP3 diffuses through cytosol and binds to a gated channel in the ER
52
Ca 2+ and IP3 in GPCR signalling (calcium)
Calcium ions flow out of ER down concentration gradient and activate other proteins towards a cellular response
53
Why so many steps (amplifies, provides)
Amplifies the response Provides multiple control points
54
Why so many steps (Allows)
Allows for specificity of response temporal spatial despite molecules in common
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Why so many steps (allows for coordination)
allows for coordination with other signaling pathways
56
Cellular responses include (gene, alteration)
- Gene expression * Alteration of protein function to gain or lose an activity
57
Cellular responses include (opening, alteration)
* Opening or closing of an ion channel * Alteration of cellular metabolism
58
Cellular responses include (regulation, rearragement)
* Regulation of cellular organelles or organisation * Rearrangement/movement of cytoskeleton
59
Cellular responses include (a combination)
* A combination of any of these
60
Cellular response (the transduction)
The transduction of a signal leads to the regulation of one or more cellular activities
61
Turning off the response
is important
62
All of the
signals are for a limited time: activation usually promotes the start of deactivation, so that signalling is of short period of time, ensuring homeostatic equilibrium
63
it means
the cell is ready to respond again if required
64
cAMP is broken
down by phosphodiesterase (PDE)
65
Inhibition
of specific PDE’s can also be a therapeutic approach eg Viagra - inhibits a specific cGMP-degrading PDE
66
Example
67
adrenalin stimulation of glycogen breakdown (adrenalin)
Adrenalin acts through a GPCR, activates cAMP and two protein kinases in a phosphorylation cascade
68
adrenalin stimulation of glycogen breakdown (results)
Results in active glycogen phosphorylase which can convert glycogen to glucose 1-phosphate
69
adrenalin stimulation of glycogen breakdown (amplification)
Amplification means that 1 adrenalin molecule can result in 108 glucose 1-phosphate molecules!
70
Glycogen
is a long term energy store in liver and skeletal muscle
71
Glycogen breakdown
results in glucose 1-phosphate
72
Glucose 1 phosphate
is then converted to glucose 6-phosphate which can then be used in glycolysis to generate ATP
73
Angiotensin-converting enzyme 2 (ACE2)
is the cellular receptor for the coronavirus (SARS-CoV-2)
74

BIOSCI107 (9 decks)

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