How cells communicate Flashcards
Why do cells communicate?
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)
What is Local signaling:
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)
What is Long distance signaling:
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.
What are other names for Signaling molecule/protein
Ligand/1st degree messenger
What are the 3 main steps of cell signaling?
Reception
Transduction
Response
During the transduction pathway multiple proteins may be activated via what?
Phosphorylation
What happens during Reception
Signalling protein (primary messenger) binds to a receptor protein
Results in shape and/or chemical state change in the receptor protein
What happens during transduction
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
What happens in Response
All of the activated proteins cause one or more functions to occur in the cell- This is where the cell actually does something
Receptors are specific!- what an analogy to remember this
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
Exquisite control is possible meaning?
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.
Receptors for water soluble molecules are …
membrane bound
eg. G Protein Coupled Receptor, Receptor Tyrosine Kinase, ligand-gated ion channel
Receptors for 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
Transmembrane proteins – pass PM how many times?
7
How many GPCRS exist and do they have similar functions?
Hundreds of different GPCRs exist
Many different ligands
Diverse functions:
eg. development, sensory reception (vision, taste, smell)
GPCRs couple with G proteins
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)
G-protein coupled receptors (GPCRs) 4 steps
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
Ligand gated ion channels/receptors
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−)
What is a receptor
a molecule/protein which responds to a specific ligand
What is a ligand/signaling protein
a signalling molecule that binds specifically to another protein
What is an ion channel
membrane protein through which specific ions can travel
What is an ion channel receptor
membrane protein through which specific ions can
travel, in response to ligand binding (also known as ionotropic receptors)
Ligand gated ion channels/receptors process
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
Which body system relies heavily on ligand gated ion channels?
The nervous system:
– released neurotransmitters bind as ligands to ion channels on
target cells to propagate action potentials
What are Signal Transduction Pathways
Signals relayed from receptors to target molecules via a ‘cascade’ of molecular interactions
What is a Protein kinases
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
What are phosphates
enzymes that dephosphorylate (remove
the phosphate) rendering the protein inactive, but recyclable
What residues are typically phosphorylated
Typically, it is serine or threonine residues that are phosphorylated.
This means that mutations affecting these residues could be detrimental.
Use of a second messenger - cAMP
Sometimes another small molecule is included in the cascade, these are second messengers.
eg. cAMP and calcium ions, ip3
The activated enzyme is …
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!
Second messenger; Low [Ca2+ ]
inside cell (typically ~100nm)
Second messenger; Very high [Ca2+ ]
outside the cell
(more than 1000-fold higher)
Maintenance of concentration via calcium
pumps is important
out of cell
-into ER
-into mitochondria
Ca 2+ and IP3 in GPCR signalling
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
Why so many steps?
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
Examples of a cellular response include activation or regulation of
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
Turning off the response is important!!
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
Sometimes its useful to generate a lot of ATP quickly!!
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
receptors can be deceived…
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
