Lecture 11-Cell signalling Flashcards
9.1 Principles of cell signaling 9.2 Distance between cells
How Do Cells Communicate
Where do all cells process information from?
Communication is most often via?
what are the specific receptor that chemical signals bind to?
where do the signals come from?
Examples of molecules that act as signals
All cells process information from the environment
* Communication required for coordination of activities
* Communication most often via chemical signals that
bind to specific receptors
– Hormones, neurotransmitters, CO2, H+
* Signals can come from outside the organism, or from neighboring cells; short distances or long
* Examples of molecules that act a signals:
* Plants:
– Ethylene
* Animals:
– Epinephrine
Examples of molecules that act as signals
Plants- Ethylene
Animals-Epinephrine
Receptor
protein that receives and
interprets information carried by signaling
molecule (ligand)
Receptor Activation and Receptor Types
What is a receptor?
where does ligand bind and what happens?
what activates receptor?
where can recepetors be found?
- Receptor: protein that receives and
interprets information carried by signaling
molecule (ligand) - Ligand binds to ligand-binding site on receptor–>conformational shape change in the entire receptor
- Shape change activates receptor
- Receptors can be found on:
– inside the cell = intracellular receptors
– cell surface = cell surface receptors
Intracellular Receptors, and which signaling molecules used? polar or non polar
Receptor+?
where are the steriod-receptor complexes located?
what do active steriod-receptor complexes act like
– Found inside the cell
– Receptor + ligand (if steroid) =
steroid–receptor complex
* Either in cytoplasm or nucleus
Which signaling molecules used
– Use non-polar signaling molecules:
* Small and pass freely through plasma membrane
* Can be a steroid
* Steroids are hydrophobic; pass through plasma membrane
* Active steroid-receptor complexes act as transcriptional
regulators and control gene expression
what do active steroid-receptor complexes act as?
transcriptional regulators and control gene expression
Cell Surface Receptors what is the general structure? and which signaling molecules used? and what three groups of cell surface receptors are there?
General structure:
1. Ligand-binding site
2. Extracellular domain
3. Transmembrane domain
4. Cytoplasmic domain
Which signaling molecules used
Use polar signaling molecules
– Small polar proteins, cannot cross
plasma membrane
Types of cell-surface
receptors:
– There are thousands of different receptor proteins on
the surface of any given cell.
– Most can be placed into one of three groups,
according to the way they are activated.
* G protein-coupled receptors
* Receptor kinases
* Ion channels
Cells surface receptor act like molecular switches and exist in which alternative states?
what happens when signalling molecule is bound to receptor?
what happens when signalling molecule is not bound to receptor?
– Many receptors exist in two alternative states – on or off
– Signaling molecule bound to receptor–>receptor activated (i.e. on)
– Signaling molecule not bound to receptor–> receptor inactive (i.e. off)
Steps that occur after signaling molecules binds to receptor
1.Receptor Activation
2.Signal Transduction
3.Cellular response
4.Termination
1.Receptor activation- receptor is turned on or activated signaling molecules activates receptor by causing conformational shape change
2.once activated ,receptor often triggers signal transduction
-> one molecule activates the next molecule which activates the next (chain reaction)
3. cellular response–> takes different forms depending on nature of signaling molecule and type of responding cells
4. termination cellular response- is stopped (cellular response can be terminated at any time in the signaling pathway) termination protects cell from overreacting to existing signals, also frees up the cell allowing it to respond to ne signals (also hold cellular response to appropriate level)
When do signal transduction, sometimes amplification response and termination occur?
These are steps that occur
after a signaling molecule binds to receptor
– Although the ligands are different, the subsequent steps
are similar
Cell surface Receptors
1.G-Protein coupled receptors
2.Receptor Kinases
3.Ion Channels
1.G-Protein coupled receptors
General Structure?
L
T
G
Types of Signal molecules used in G protein Couples Recetors?
Transmembrane proteins with this general structure:
Ligand binding site – extracellular
Transmembrane region - 7 alpha helices
G-protein binding site-cytoplasmic
Slide 10
G Protein-Coupled Receptors
* Types of signal molecules used
by G-protein-coupled receptors:
* Small molecules
* Many hormones
* Neurotransmitters
* G-protein-coupled receptors
are responsible for senses of
sight, smell, taste
What are G-protein-coupled receptors
are responsible for
senses of
sight, smell, taste
Cell surface Receptors
1.G-Protein coupled receptors
2.Receptor Kinases
3.Ion Channels
1.G-Protein coupled receptors
what happens when ligand binds to G protein coupled receptor?
When active it binds to?
The G protein binds to?
G protein + ?=inactive
G Protein +?= active
Summarize
WHat can G protein do as part of singalling pthway
When ligand binds to G protein-coupled receptor, it is
activated
* When active, it binds to a G protein (cytoplasm)
* G proteins can be bound to either GDP or GTP (guanine nucleotides)
* G protein + GTP = active
* G protein + GDP = inactive
* Ligand binds–>receptor then binds to G protein–>GDP replaced with GTP and G protein activated–>signal transmitted
– Active G protein then activates other proteins as part of
signaling pathway
Steps of Ligand binding in G-Protein coupled receptors
Ligand binds–>receptor then binds to G protein–>GDP replaced with GTP and G protein activated–>signal transmitted
– Active G protein then activates other proteins as part of
signaling pathway
What are some G proteins composed of?
α (alpha)
β (beta)
γ (gamma)
* α (alpha) subunit binds either GDP
or GTP
* α subunit + GDP–> 3 subunits bound =inactive
* Receptor activated–> GDP on α
subunit replaced by GTP–> 3 subunits separate = active
* Activated α subunit binds to and
activates target protein–> response
Example of G Protein Activation and
Amplification:
Adrenaline Signaling in Heart Muscle
ACTIVATION
(Start from target protein end at- heart rates increases)
Target protein = adenylyl cyclase–>
Activated adenylyl cyclase converts
ATP to cAMP (second messenger)–>
cAMP binds to Protein kinase A–>
Activated protein kinase A
phosphorylates heart proteins–>
Heart rate increases
Example of G Protein Activation and
Amplification:
Adrenaline Signaling in Heart Muscle
AMPLIFICATION
Keypoints
cell response depends on?
G-protein coupled receptors activate which way?
The effects of amplication are?
A little adrenaline goes a
long way!
* Amplification occurs at
several places (1, 2, 3)
* Small amount of signal–>
large response
Key Point:
* Cell response depends on cell
type and proteins in it
* G protein-coupled receptors
typically activate downstream
enzymes or open ion channels
* Effects are rapid, short-lived,
reversible
Termination of G protein Signal
The amount of time a signalling molecule remains bound to it receptor depends on?
Do most ligands bind permenantly to receptors?
When does signals turn off?(GTP –> GDP)
Enzymes degrade from __ to ___ ?
Phosphatases?
when happens when an enzyme is dephosphorylated
The amount of time a signaling molecule remains bound to
its receptor depends on how tightly the receptor holds on to
it, its binding affinity for the signaling molecule.
* Most ligands do not bind permanently to receptors
* Signal turns off once ligand is unbound (G protein deactivates itself)
* GTP to GDP
* Other parts of the pathway must also turn off
* Enzymes degrade cAMP to AMP
- Phosphatases remove phosphate group = dephosphorylation
- When a protein is dephosphorylated by a phosphatase, it
typically becomes inactive
Phosphatases
when phosphate group is removed(dephosphorpylated) it typically becomes active or inactive?
remove phosphate group = dephosphorylation
* When a protein is dephosphorylated by a phosphatase, it
typically becomes inactive
Cell surface Receptors
1.G-Protein coupled receptors
2.Receptor Kinases
3.Ion Channels
Receptor Kinases
what’s a kinase?
wheredoes phosphate group come from?
What happens when protein is phosphorylated by a kinase?,what occurs?
Quick recall kinase vs phosphatases
A kinase is an enzyme that adds
a phosphate group to another
molecule–> phosphorylation
* Phosphate group comes from
ATP
* When a protein is phosphorylated by a kinase, that protein
typically becomes active
– Shape change or
– Provides new site for other
proteins to bind
* Recall: phosphatases have the
opposite effect i.e. remove
phosphate group =
dephosphorylation
Receptor Kinase Activation/Transduction
extracellular portion
intracellular portion
Dimerization
phosphorylated areas provide?
- Extracellular portion - binds signaling molecule
- Intracellular portion - is the kinase
- Dimerization activates cytoplasmic kinase domains causing
them to phosphorylate each other at multiple sites on their
cytoplasmic tails. - Phosphorylated areas provide sites for other proteins to bind
and become active.
Extracellular portion
binds signaling molecule
Intracellular portion
is the kinase
Dimerization
activates cytoplasmic kinase domains causing them to phosphorylate each other at multiple sites on their
cytoplasmic tails.
Where is receptor kinase signaling used?
(in the formation and elongation of?, cut, activation of? cells?)
Do receptor kinases intiatie long term or short term responses?
*Formation and elongation of limb buds that
become our arms and legs
*Wound healing
* when we cut ourselves, platelet derived growth factor
(PDGF) released from platelets in the blood signals to
cells at the wound site, triggering cell division to repair
the damage
*In general, receptor kinases initiate long-term
responses
* Activation of proteins involved in changes in gene
expression
* Cell growth, division, differentiation, shape change
receptor kinases initiate long-term
responses
* Activation of proteins involved in changes in gene
expression can cause
Cell growth, division, differentiation, shape change
Receptor Kinase Example: The MAP kinase pathway
Paper cut – ouch!–>
Platelets release proteins
including PDGF–>
PDGF binds to receptor
kinases on cell surface–>
Dimerization; receptor
activation–>
Ras protein activated (in
cytoplasm); GTP bound–>
Kinase series triggered;
kinase enters nucleus–>
Transcription regulators for
cell division activated
*This pathway becomes
inactive once the GTP bound Ras is converted
to GDP
Receptor Kinases
A receptor kinase, Kit, responsible for?
the production of pigment in skin, feathers, scales and hair
Mutations in the Kit receptor kinase causes?
patterns of incomplete pigmentation (white patches)
Cell surface Receptors
1.G-Protein coupled receptors
2.Receptor Kinases
3.Ion Channels
3.Ion Channels
what do ion channels alter?
what does the conformational shape change allow?
Channel remains open as long as?
These are receptors that alter
flow of ions across plasma
membrane (channels)
* Conformational shape
change opens channel
– Allows flow of ions in and/or out
– Channel remains open as long
as the signaling molecule
remains bound
Integration of Signaling Pathways
Do signalling pathways operate independtly?
Different signaling molecules can do what?
final response of a cell depends on?
one signal may inhibit signaling pathway and do what to the end response?
Signaling pathways do not operate independently –
signaling is very complex!
– In one organism - many different signaling molecules
each with own receptors
* Different signaling molecules can bind to a single cell
and activate several signaling pathways simultaneously
– final response of a cell depends on how the pathways
intersect with one another
* Also, one signal may inhibit signaling pathway
triggered by a another signal and weaken the end
response
* “Molecular cross-talk”
9.1 Principles of cell signaling
one key source from where cells receive their info
cells receive lots of info,
one key source is physical environment and other cells, neighboring, nearby and distant both multicellular and unicellular respond to info by changing their activity
General principles of cell communication- cells communicate using chemical signals that bind to receptors
(apply to all cells, prokayrotic, eukaroytic multicellular and unicellular)
Cellular communications consist of which 4 elements
1)signaling molecule
2)signaling cell
3)receptor protein
4)responding cell
Signaling molecule
which hormone?
where is it released from?
is the hormone adrenaline (also called epinephrine) in response to stress adrenaline is released from adrenal glands (located above kidney) adrenaline circulates the body, and acts on many types of cells- cells of heart to cause it to beat more strongly and quickly as a result the heart is able to deliver oxygen more efficiently throughout body
Signaling
when does it occur?
Steps (starts from receptor activation ends from termination)
what does termination protect from and allow?
Occurs after signaling molecule binds to receptor
1.receptor activation receptor is turned on activated, the signaling molecule activates the receptor by causing conformational shape change
2.signal transduction, once activated receptor triggers signal transduction, which is when one molecules activates the next which activates the next (chain reaction)
3.cellular response takes different responses depending on the nature of signaling molecule and type of responding cell
4. termination- cellular response is stopped (Cellular response can be terminated at any point in signaling pathway) termination protects cell from overreacting to existing signals, also frees up the cell allowing it to respond to new signals (also holds cellular response to appropriate levels)
response of a cell to signalling molecule depends on?
when do cells only respond to signal:
when does downstream effect occur
cell type
cells exposed to many different types of signaling molecules cells only respond to signal if receptors are able to bind to signaling molecules
if specific receptors are present binding of signaling molecules will lead to downstream effect, if specific receptors are not present cell will not be able to respond
ADRENALINE
where are adrenaline receptors?
what does it cause(heart muscle vs cells lining)?
only cells with receptors for adrenaline are able to respond adrenaline receptors are widespread in body heart, lung stomach presence of this receptors allow the cell of these organ’s respond to adrenaline
cause heart muscle cells to contract more quickly and forcefully whereas causes cells lining in the airway of lung to relax
what determines specific response of cells?
on the set of proteins in the cell and signaling pathways within the cell
Diff cell type= diff sets of intracellular proteins and signaling pathways result same signaling molecule can have diff effects in diff types of cells
Distance between cells prokaryotes & unicellular eukaryotes what is the cell communication between?
cell communication is between individual organisms
Distance between cells complex multicellular eukaryotes cell communication occurs between?
between cells within the same organism
Signaling molecules released by cell that travel great distances to reach receptor cells in this case often carried in circulatory system
travel through bloodstream
Endocrine signaling (adrenaline- epinephrine)
carried by bloodstream to target cells that are far from signaling cells
signalling that occurs over short distances
signalling that occurs between two cells that are close together to one another diffusion between two cells instead of using circulatory system
paracrine system
(signal takes form of small water soluble molecule such as growth factor(type of signaling moecule that causes responding cell to grow, divide, differentiate)
Important to multicellular organisms during development embryo
signaling molecules may be released by a cell and then bind to receptor on the same individual cell?
Autocrine signalling
contact-dependent, direct contact without diffusion or circulation of signaling molecule, two communication cells can be in physical contact with each other (important during development of central nervous system)
Contact-dependent signaling
