How cells communicate

Question 1

Why do cells communicate?

Answer 1

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

Question 2

What is Local signaling:

Answer 2

Signals act on nearby target cells

• growth factors such as fibroblast growth factor – FGF1
  (paracrine)
• Neurotransmitters such as acetylcholine – ACh
  (synaptic)
• Can act on the signaling cell (autocrine)

Question 3

What is Long distance signaling:

Answer 3

Signals act from a distance

• Hormones secreted from endocrine cells travel via circulatory
  system to act on target cells
  eg. insulin secreted from pancreatic beta cells enters bloodstream
  and travels and is detected by various body cells.

Question 4

What are other names for Signaling molecule/protein

Answer 4

Ligand/1st degree messenger

Question 5

What are the 3 main steps of cell signaling?

Answer 5

Reception
Transduction
Response

Question 6

During the transduction pathway multiple proteins may be activated via what?

Answer 6

Phosphorylation

Question 7

What happens during Reception

Answer 7

Signalling protein (primary messenger) binds to a receptor protein
Results in shape and/or chemical state change in the receptor protein

Question 8

What happens during transduction

Answer 8

Altered receptor activates a another protein, eg G-protein/adenylyl cyclase
The activated protein (often an enzyme) may cause a relay of changes
Relay molecules known as “second messengers”, eg. cAMP, IP 3
Multiple other proteins may be activated
Each activated protein causes a series of changes, this is often via
phosphorylation – known as a phosphorylation cascade

Question 9

What happens in Response

Answer 9

All of the activated proteins cause one or more functions to occur in the cell- This is where the cell actually does something

Question 10

Receptors are specific!- what an analogy to remember this

Answer 10

use of fork, spoon & knife

Structure determines function

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

Question 11

Exquisite control is possible meaning?

Answer 11

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.

Question 12

Receptors for water soluble molecules are …

Answer 12

membrane bound

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

Question 13

Receptors for lipid soluble molecules are//

Answer 13

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

Question 14

Transmembrane proteins – pass PM how many times?

Answer 14

7

Question 15

How many GPCRS exist and do they have similar functions?

Answer 15

Hundreds of different GPCRs exist
Many different ligands
Diverse functions:
eg. development, sensory reception (vision, taste, smell)

Question 16

GPCRs couple with G proteins

Answer 16

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)

Question 17

G-protein coupled receptors (GPCRs) 4 steps

Answer 17

1-At rest, receptor is unbound and G
Protein is bound to GDP.
The enzyme is in an inactive state

2-Ligand binds receptor, and binds the G protein. GTP displaces GDP. The enzyme is still inactive. -shape change

3-Activated G Protein dissociates from receptor. Enzyme is activated to elicit a cellular response

4-G Protein has GTPase activity,
promoting its release from enzyme,
reverting back to resting state

Question 18

Ligand gated ion channels/receptors

Answer 18

These channel receptors contain a “gate”

channel opens /closes as the receptor changes shape

Binding of ligand (eg neurotransmitter) at specific
site on receptor elicits change in shape

ions can pass through channel (eg. Na+ , K+ , Ca 2+ , and/or Cl−)

Question 19

What is a receptor

Answer 19

a molecule/protein which responds to a specific ligand

Question 20

What is a ligand/signaling protein

Answer 20

a signalling molecule that binds specifically to another protein

Question 21

What is an ion channel

Answer 21

membrane protein through which specific ions can travel

Question 22

What is an ion channel receptor

Answer 22

membrane protein through which specific ions can
travel, in response to ligand binding (also known as ionotropic receptors)

Question 23

Ligand gated ion channels/receptors process

Answer 23

1- At rest, ligand is unbound
and gate is closed.

2- Upon ligand binging, gate opens,
specific ions can flow into cell.

3- Following ligand
dissociation, gate closes,
back to resting

Question 24

Which body system relies heavily on ligand gated ion channels?

Answer 24

The nervous system:
– released neurotransmitters bind as ligands to ion channels on
target cells to propagate action potentials

Question 25

What are Signal Transduction Pathways

Answer 25

Signals relayed from receptors to target molecules via a ‘cascade’ of molecular interactions

Question 26

What is a Protein kinases

Answer 26

are enzymes that transfer a phosphate
group from ATP to another (specific) protein. Typically, this
activates the protein

Series of protein kinases each adding a phosphate to the
next kinase

Question 27

What are phosphates

Answer 27

enzymes that dephosphorylate (remove
the phosphate) rendering the protein inactive, but recyclable

Question 28

What residues are typically phosphorylated

Answer 28

Typically, it is serine or threonine residues that are phosphorylated.
This means that mutations affecting these residues could be detrimental.

Question 29

Use of a second messenger - cAMP

Answer 29

Sometimes another small molecule is included in the cascade, these are second messengers.
eg. cAMP and calcium ions, ip3

Question 30

The activated enzyme is …

Answer 30

adenylyl cyclase
Activated adenylyl cyclase converts ATP to cAMP

cAMP acts as a second messenger and activates downstream
proteins, for example, PKA which phosphorylates other proteins

This pathway is disrupted by cholera toxin!

Question 31

Second messenger; Low [Ca2+ ]

Answer 31

inside cell (typically ~100nm)

Question 32

Second messenger; Very high [Ca2+ ]

Answer 32

outside the cell
(more than 1000-fold higher)

Question 33

Maintenance of concentration via calcium
pumps is important

Answer 33

out of cell
-into ER
-into mitochondria

Question 34

Ca 2+ and IP3 in GPCR signalling

Answer 34

Here, the activated protein is
phospholipase C which then
cleaves PIP2 (a phospholipid) into
DAG and IP3

IP3 diffuses through cytosol and
binds to a gated channel in the ER

Calcium ions flow out of ER down
concentration gradient and activate
other proteins towards a cellular
response
Muscles use Ca2+ to contract

Question 35

Why so many steps?

Answer 35

Amplifies the response
Provides multiple control points
Allows for specificity of response
temporal
spatial
despite molecules in common
Allows for coordination with other signaling pathways

Question 36

Examples of a cellular response include activation or regulation of

Answer 36

Gene expression
* Alteration of protein function to gain or lose an activity
* Opening or closing of an ion channel
* Alteration of cellular metabolism
* Regulation of cellular organelles or organisation
* Rearrangement/movement of cytoskeleton
* A combination of any of these
The transduction of a signal leads to the regulation of one or more cellular activities

Question 37

Turning off the response is important!!

Answer 37

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

it means the cell is ready to respond
cAMP is broken down by phosphodiesterase (PDE)
eg. caffiene blocks PDE

Inhibition of specific PDE’s can also be a therapeutic approach
eg Viagra - inhibits a specific cGMP-degrading PDE

Question 38

Sometimes its useful to generate a lot of ATP quickly!!

Answer 38

Glycogen is a long term energy store in liver and skeletal muscle
glycogen breakdown results in glucose 1-phosphate
glucose 1-phosphate is then converted to glucose 6-phosphate which can
then be used in glycolysis to generate ATP

Question 39

receptors can be deceived…

Answer 39

Angiotensin-converting enzyme 2 (ACE2) is
the cellular receptor for the coronavirus
(SARS-CoV-2)

surface spike glycoprotein (S protein)
ACE2 in our respiratory tract is the
lock, and the S-protein on the virus is the key