19 – Cells & their environment II: Short-term signals Flashcards
Chemical signals received by
cell surface receptors
-Cell surface receptors embedded to plasma membrane
Cellular response can be
short term or long term
Short term
Modification of cellular metabolism/function/movement
Rapidly executed/inactivated
-NOT all or nothing
-Can be turned up/down in response to change in concentration of signaling molecule in blood
Long term = irreversible
Modification of gene expression/development
Time frames less critical
Decision more critical: all or nothing
Endocrine signaling:
Hormone secretion into blood by endocrine gland = travel through blood vessel = target distant cells
Ligands bind to receptors = according to
chemical equilibrium
Response of cell often more
sensitive than anticipated
-Physiological response = how much have cells reacted to presence of hormones
-Cells have way of sensitizing themselves to signal
–Cells fully react to hormone when only a fraction of their receptor is bound
Adrenaline (epinephrine), what happen to your body?
hormone triggers short term responses
-Cardiac muscle = increase contraction
-Liver = conversion of glycogen to glucose, inhibition of glycogen synthesis
-Skeletal muscle= conversion of glycogen to glucose
-Start getting body ready to make lots of ATP
GPCRs
G-protein coupled receptors
respond to many hormones signals
made of 7 transmembrane helices
recognize adrenaline
binding of adrenaline to cell surface receptors triggers
triggers changes in metabolism
how does GPCRs respond to hormone signals/know the ligand is bound? step by step
- When ligand binds into basket
- Basket torqued/twists/misshapen by binding to ligand
- Change in conformation of intracellular/cytoplasmic face
- Cells know ligand is bound
G-proteins
trimeric GTPases = transduce hormone signals
o GDP-bound off state
o GTP-bound on state
Activated = transduce signal downstream
nucleoptide binding pocket: Switch I & II = conformational change because it has to come inward to interact with the phosphate
mechanism of Hormone binding to GPCR
- Inactive receptor binds with hormone- induce conformational change = active receptor
-Distortion of basket - change in shape of intracellular face
-Hormone binding to GPCR = recruit G-protein - G-protein binds to GPCR & becomes activated
- Activated receptor binds to G-alpha subunit
- Binding of GTP to Ga triggers dissociation of Ga from receptor & Gby
* Ligand binds to receptor
* Receptor changes shape
* G-protein sticks
* Gets immediately knocked off - Active G-protein transduce signal to an effector protein
-Hormone dissociates from receptor & Ga binds to effector to activate it - Hydrolysis of GTP to GDP = Ga dissociate from effector & reassociate with Gby
-Effectors kick off Ga = bounce back & forth between effectors
G alpha bind to receptor =
switched on
G alpha bind to effector
switched off
when there is adrenaline, what happens to your cells?
abunch of G-alpha proteins are bouncing back and forth between effector molecules & adrenaline receptors
what happens when no more adrenaline?
eeffector will turn on G-alpha, but it doesnt have anything to turn itself back on again = resting state with trimeric G-protein
FRET
Forster resonance energy transfer determine if 2 molecules are within nanometers (physical distance)
how does FRET work
Excites CFP= fluorescence by YFP (yellow) = only if G-proteins very close together
within seconds of ligand-binding
Heterotrimeric G-protein = dissociation of Ga and Gby
-YFP no closer to CFP = cyan color instead
Adenylyl cyclase
common effector of activated G-proteins & makes cAMP
cAMP
second messenger
-activates Protein Kinase A
-active PKA – catalytic subunits & regulatory subunits dissociates = it can now go phsphoarylate
PKA
Protein kinase A -
directly controls molecules of glycogen metabolism when active
-Stimulation of glycogen breakdown
-Inhibition of glycogen synthesis
Multistep activation result in
significant amplification of the signal
-Because of amplification = response of cells = often more sensitive!!
Even when less surface receptors are bound = more physiological response
a single epinephrine bound to a receptor would produce many active G alpha components which would ping
out to bind to adenyl cyclase.
That adenyl cyclase while activated, would produce a lot of cyclic AMP.
That cyclic AMP would in turn activate a lot of protein kinase A, it phosphorylate many enzymes leading to a amplification of the product.
So even though we only had a very low concentration of adrenaline or epinephrine, you could see a significant relative increase in the concentration of cyclic amp/
