Week 10: Cell signaling Flashcards
why do cells signal? (3)
- survive
- grow/divide
- differentiation
why do cells need signals to survive?
without this they undergo apoptosis
- In humans with aging, its partly because neuronal cells are dying in the brain and so is their communication
- Any severance in spinal cord causes permanent paralysis because apoptosis is triggered in those neurons
why do cells need signals to grow/divie?
cell division is constantly happening all the time
- Constantly shedding cells
- When this is blocked we have many major issues in the body with bad side effects
why do we need signals for cells to differentiate?
stem cells and blood cells are constantly being generated (blood cells start out as stem and then differentiate)
4 types of cell communication?
- contact dependent
- paracrine
- neuronal
- endocrine
contact dependent signaling
exchange information with neighbors through the cells physically touching one another to pass on the signal
paracrine signaling
share information with cells in the neighborhood with limited distance
neuronal signaling
share information with cells in another organ/tissue through a physical communication over a large distance by synapsing on them
endocrine signaling
share information with cells across the body like a broadcast through the bloodstream
what acts as signals?
hormones, touch, light, odorants come from outside or inside
how do cell decode signals?
The cells have receptors which could be on the surface or the inside of the cell
- This is what receives the signal
- Results in a cellular response
features of signaling (4)
- diverse signaling molecules
- different cells respond differently
- response can be fast or slow
- receptors can be inside the cell or cell membrane
hormones
released into the bloodstream and consist of different types of signals such as immediate or over a long time to change the metabolic state of the body
types of hormone molecules?
steroids, proteins, peptides, and amino acid derivatives
catecholamines
come from amino acid derivatives
example of an immediate hormonal signal?
adrenaline (epinephrine) => increases blood pressure, heart rate, and metabolism
example of a longer time hormonal signal?
cortisol => affects metabolism of proteins, carbohydrates, and lipids in most tissues
Nitric oxide
come from nerve and endothelial cells that line blood vessels
- is a dissolved gas
- causes smooth muscles to relax and regulates nerve cell activity as a local mediator
acetylcholine
comes from nerve terminals and is an excitatory neurotransmitter at nerve-muscle synapses and in the CNS
GABA (gamma aminobutyric acid)
comes from nerve terminals and inhibits inhibits neurons in the CNS as a neurotransmitter
what is delta?
a transmembrane protein that makes a physical connection with another molecule to trigger the signal and inhibits neighboring cells from becoming specialized like the signaling neuron or developing cell
what is a common trend for local signaling molecules, neurotransmitters, and contact dependent signaling molecules?
they are essential for growth which stimuli the cell to grow and divide
what 3 cells does acetylcholine act on?
small protein
1. pacemaker heart cells => decreased firing
2. salivary gland cells => secretion
3. skeletal muscle cells => contraction
how does acetylcholine affect heart pacemaker cells?
when secreted it acts on the pacemaker cells of the heart to allow for contraction
- There is a receptor that binds it which decrease the rate
how does acetylcholine affect salivary gland cells?
It can bind to the receptor in the gland cell which increases secretion allowing you to digest your food
- same receptor as heart pacemaker cell
how does acetylcholine affect skeletal muscle cells?
can also bind to skeletal muscle cells and cause the cells receptor to have a different shape which triggers a different receptor ⇒ it causes the skeletal muscle cells to contract
what does context matter mean for cell signaling?
different cells respond differently to the same signal depending on receptor, intracellular signaling pathway, and history ⇒ if the same cell gets the same signal twice it may not respond the same
how does a signal change cell responses? (2)
- Change the function of existing proteins ⇒ doesn’t change the circuit but triggers a response
- Results in fast response - The signal may go into the nucleus to affect transcription which makes new proteins
- Altered protein synthesis changes what the cell is by changing its constitution (physiologically)
- This takes time because DNA ⇒ RNA ⇒ protein
where can cell receptors be?
on the inside or outside membrane of the cells
hydrophilic signals
bind to cell surface receptors ⇒ likes to be water soluble so the cell membrane will exclude this without a transporter
hydrophobic signals
crosses bilayers and bind intracellular receptors because the lipid bilayer lets it through
- often goes to the nucleus of the cell to act on the individual genes
how does bovine serum albumin affect your cell responses?
BSA is unlikely to be in your bloodstream which would constantly trigger receptors on our cell surface, so BSA receptors are located in the cell and BSA acts as a carrier protein to transport small molecules inside of a cell
why is BSA unlikely to form a mega complex?
because it often blocks nonspecific reactions
what molecules is the cell membrane permeable to?
- small hydrophobic gasses
- small uncharged molecules
what molecules are not permeable on the cell membrane?
- large polar molecules unless they have a transporter
- charged ions because they would depolarize the membrane and cause loss of the electrochemical gradient
examples of small hydrophobic molecules?
O2, CO2, N2, benzene
examples of small uncharged molecules?
H2O, glycerol, ethanol
examples of larger polar molecules?
amino acids, glucose, nucleosides
examples of ions?
H+, Na+, HCO3-, K+, Ca2+, Cl-, Mg2+
what are intracellular receptors?
steroid hormone derivatives of cholesterol or tyrosine
- they are hydrophobic, cross the bilayer, and affect intracellular receptors
- These are hydrophobic and often have carbon rings which are not water soluble
examples of intracellular signals
Cortisol, estradiol, testosterone, and thyroxine are derivatives (often have “ol” at the end of name
steps of hormone signaling (5)
- Cross membrane
- Bind intracellular receptor ⇒ this induces a conformational change in the protein which can localize through the nuclear pore to activate target gene transcription
- It could also go all the way through and bind to a receptor inside of the nucleus - Receptor may be in cytoplasm or nucleus
- If cytoplasmic, hormone binding stimulates movement to nucleus
- Activate transcription
nitric oxide properties in capillaries
made in endothelial cells (line capillaries) diffuse into smooth muscle cell ⇒ these are the first line of defense in the capillary cells
- These sit on the basal lamina matrix
- On the other side there are the smooth muscle cells ⇒ have a mesh of actin and myosin to allow contraction to happen but no sarcoplasmic reticulum
- NO is a natural regulator of smooth muscle relaxation
When cells contract the capillaries close and vice versa
hypertension
people with their capillaries naturally more contracted due to vasoconstriction so they need medications to help their smooth muscle cells relax
- This lets blood to the periphery which reduces pressure on your heart
what does NO bind to in the pathway shown in class?
it binds to guano cyclase (first messenger) which takes guanosine triphosphate and cyclizes it to produce cyclic GMP which is a second messenger to help smooth muscle cells relax
viagra process
blocks cGMP phosphodiesterase, which prolongs relaxation of smooth muscle, promotes dilution of blood vessels in the penis, leading to penile erection
Takes away cyclization so you get an increase in their molecules
what is the cell surface receptor process? (3)
- receptor
- cascade
- downstream response
signaling cascade/pathway
one thing triggers the next and so on ⇒ can become downstream
- Important to know differences between normal cells and unhealthy cells
what makes up the downstream response (3)
- metabolism
- trascription
- cytoskeletal proteins
opsin
in your eye are single photon sensitive for detecting light ⇒ one rhodopsin molecule absorbs one photon
- This activates up to 500 G-protein molecules as a second step
- Each G-protein can activate 500 cyclic GMP molecules
- This leads to 105 cyclic GMP molecules being hydrolyzed
what does opsin demonstrate?
we are extremely sensitive to low levels of substances because we need our bodies to produce a dramatic response => such as to toxins
class 1 receptors
ligand gated ion channels
ligand gated ion channels
Signal (ligand) binding regulates opening or closing of ion channel, ion flow, membrane potential, etc. to convert chemical signals into electrical signals ⇒ the electrical signal comes from the ions and where they are on the cell membrane sides
what is the signal in the ligand gated ion channels nd what is the ultimate effect?
The signal could be the ion itself or it could be a different signal opening the channel that lets the ions flow
- Ultimate effect is always the ion channel permeability being changed
- Depending on which ion, a selective ion channel only lets certain things cross
class 2 receptors
G-protein coupled receptors
G-protein coupled receptors
large and widespread receptors that use transmembrane alpha helices and activate or inhibit other proteins such as enzymes
- Ligand binding activates membrane bound G-proteins
- Activated G-protein actives or inhibits target proteins
what is an example of a class 1 receptor?
the second part of the calcium induced calcium release when calcium binds another receptor to release more calcium from the sarcoplasmic reticulum
class 3 receptors
enzyme coupled receptors aka often receptor tyrosine kinases (RTKs)
enzyme coupled receptors
have a signal in the form of a dimer which can allow the two proteins to activate one another (usually phosphorylation) and ultimately activates an associated enzyme
properties of class 3 receptors? (3)
- Intracellular domains are bound to enzymes (usually kinases)
- Prominent in multicellular organisms
Single pass, transmembrane proteins that dimerize or associate with another enzyme after activation
diversity in cell signaling
by mixing and matching types of receptors and factors you get a whole different set of responses in response to ligands
modular system
can combine the different parts of the system to get diversity in how a cells response comes out to suit its purposes
key features of signaling pathways
cell signaling can act as boosters upstream and downstream responses are modulated
2 ways that proteins signals are turned on and off?
- protein phosphorylation and phosphatase
- GTPase switches from GDP to GTP and vice versa
protein phosphorylation
protein goes on and it gets phosphorylated by a protein kinase (ATP used) and this creates a signal turned on (usually)
phosphatase
cleaves off a phosphate group and turns a signal off (usually)
GTP switches
in the GDP bound state until a signal causes GDP to be exchanged for GTP (on state) which allows they protein to act as a GTPase to act like a timer for hydrolysis eventually to shut the switch off
- like a timer
positive feedback
a signal kinase will phosphorylate another kinase which goes on to tag another kinase in a chain reaction to create positive feedback
- until phosphatase causes the signal to shut off
- when there is positive feedback the signal stays on after the initial signal because the kinases are still triggering one another until phosphatase catches up
all or none response
you only have to activate enough kinases in a small concentration to activate the entire population of signals
It can boost the signal with a small amount of signal coming out
- You can see it in the way cells response because some will fully activate at what appears to be a random pattern
negative feedback
a signal kinase will go on to activate an enzyme and the enzyme activates a phosphatase so the enzyme works against itself to shut the signal off
- To work, there must be some delay between activation of the enzyme and activation of the phosphatase or you won’t ever see a signal at all
differences in negative feedback over short vs long?
- the short signal will jump up and then oscillate 1-2 times before flatlining and going back down => called an attenuated signal
- vs. the longer signaling delay will oscillate up and down constantly before being shut off
how are drugs like signaling molecules?
they can mimic signaling molecules or block their action
- nicotine, morphine, heroin, curare, strychnine
