Chapter 16: Cell Signaling Part 2 Flashcards
1
Q
G-protein
A
- membrane bound GTP-binding protein involved in intracellular signaling
- composed of three subunits
- intermediary usually activated by the binding of a hormone or other ligand to a transmembrane receptor
2
Q
GPCR
A
G-Protein Coupled Receptors
3
Q
G-Protein Coupled Receptors
A
- largest super family of cell surface receptors
- mediated most responses from external world(senses of sight, smell, taste)
- can be activated by a single ligand
(adrenaline, acetylcholine, serotonin)
4
Q
Describe an activated GCPR
A
- an acitvated GPCR activates G proteins by encouraging the alpha subunit to expel its GDP and pick up GTP
- signal molecule binds to active receptor, changes conformation of receptor
- alteration of alpha subunit of G protein allows it to exchange its GDP for GTP, creates additional change to activate alpha and beta-y complex
5
Q
What does the alpha and beta-y complex provide activated GPCR/G proteins once activated?
A
- two activated parts can then interact directly with target proteins in plasma membrane, may relay signal to other destinations as well
- the longer these target proteins remain bound to an activated alpha subunit, or a beta-y complex, more prolonged the relayed signal will be
6
Q
Describe the binding of GPCRs to trimeric G-proteins
A
- trimeric G proteins have 3 subunits
- when the GPCR is activated by a signlaing molecule, it activates the alpha subunit of the G protein
- causes it to release GDP and bind to GTP
- now the alpha subunit dissociates from the other subunits and both are activated
- the signal is shut off when the alpha subunit hydrolyzes the GTP to GDP
- then the alpha subunit binds to the other subunits again and the signals are shut down
7
Q
What can some membrane-bound enzymes, activated by G proteins, do?
A
- produce small messenger molecules
- once activated enzymes produce small molecules(second messengers) rapidly, molecules rapidly diffuse away from the source, amplifies and spreads to intracellular signal
- messenger molecules bind to specific signaling proteins in cell and influence activity
8
Q
Two most frequent small messenger molecules produced by membrane-bound enzymes
A
- adenylyl cyclase
- phospholipase C
9
Q
Adenylyl cyclase
A
- produces small molecule cyclic cyclase
- enzymes that catalyzes formation of cyclic AMP from ATP, important in intracellular signaling pathways
10
Q
phospholipase C
A
- produces small molecule inositol triphosphate and diacylglycerol
- enzyme associated with the plasma membrane that generates two smaller messenger molecules in response to activation
11
Q
Describe how enzyme adenylyl cyclase is activated by GPCR
A
- adenylyl cyclase makes cyclic AMP
- many activated GPCR affect adenylyl cylcase, alters intracellular concentration of 2nd messenger cyclic AMP
- adenylyl cyclase is activated by the alpha subunit of the trimeric G protein
- creates dramatic increase in synthesis of cyclic AMP to ATP
- to terminate the signal, 2nd enzyme called cyclic AMP phosphodiesterase rapidly converts cyclic AMP to ordinary AMP
12
Q
cyclic AMP
A
- small intracellular signaling molecule generated from ATP in response to hormonal stimulation of cell surface receptors
- synthesized by adenylyl cyclase and degraded by cyclic AMP phosphodiesterase
- formed from ATP by cyclization reaction that removes two phosphate groups from ATP and joins “free” end of remaining phosphate group to the sugar part of the AMP molecule
- degradation reaction breaks this new bond, forming AMP
13
Q
Describe one type of cAMP pathway, Epinephrine
A
- epinephrine stimulates glycogen breakdown in skeletal muscle cells
- hormone activates a GPCR, which turns on G protein that activates adenylyl cyclase to boost production of cyclic AMP
- adrenalin released, binds to GPCR, activates adneylyl cyclase, makes cAMP
- then cAMP activates protein kinase A(PKA): it phosphorylates another kinase, which phosphorylates another enzyme involved in breakdown from glycogen to glucose
14
Q
PKA
A
- protein kinase A
- activated by rise in intracellular cyclic AMP
15
Q
Describe how GPCR can activated cAMP pathways that regulate transcription
A
- rise intracellular cyclic AMP can activate gene transcription
- PKA, activated by intracellular cyclic AMP, can enter nucleus and phosphorylates specific transcription regulators
- phosphorylated transcription regulator proteins stimulate transcription of whole set of target genes
- examples: hormone synthesis in endocrine cells and production of proteins involved in long term memory in brain
16
Q
Describe activation of Phospholipase C
A
- GPCRs coupled to PLC which leads to increased intracellualr mediator Ca++ (inositol pathway triggers an increase)
- Ca++ activates protein kinase C (PKC)
- IP diffuses through cytosol, triggers release of Ca2+ from ER by binding and opening Ca2+ channels in ER membrane
- large electrochemical gradient for Ca2+ across membrane causes Ca2+ to rush out of ER, intro cytosol
- diacylglycerol remains in plasma membrane, uses Ca2+ alongside it to activate enzyme protein kinase(PKC)
- PKC recruited from cytosol to cytosolic face of plasma membrane, phosphorylates own set of intracellular proteins, propagating signal
17
Q
Explain how GPCRs are involved in vision
A
- GPCR based visual signaling pathways analyzed through rod photoreceptor cells in eye, responsible for noncolor vision in dim light
- Rhodopsin is GPCR
18
Q
Rhodopsin
A
- G protein, activates G protein transducin when stimulated by light
- connection to rod photoreceptors, cell from retina is quite sensitive to light
19
Q
Describe Rhodopsin process
A
- rod stimualted by light, signal is relayed from the rhodopsin molecules in the discs, through the cytosol, to cation channel in plasma membrane of outer segment
- cation channels close in response to cytosolic signal
- produces change in membrane potential
- change in memrbane potential alters rate of neurotransmitter release from synaptic region of the cell
- released neurotransmitters act on retinal nerve cells that pass signal to brain
20
Q
Adaptation
A
- adjustment of sensitivity following repeated stimulation
- allows a cell or organism to register small changes in a signal despite a high background level of stimulation
- depends on negative feedback
21
Q
negative feedback
A
- an intense response in the photoreceptor cell decreases cytosolic Ca2+ concentration, inhibiting enzymes, responsible for signal amplification
22
Q
Describe the process of light adaptation
A
- in absence of light signal, 2nd messenger molecule cyclic GMP continued to produce by guanylyl cyclase in cytosol of photoreceptor cell
- cyclic GMP binds to cation channels of plasma membrane to keep them open
- rhodopsin activated, activates alpha subunit of transducin
- transducin turns on enzyme cyclic GMP phosphodiesterase
23
Q
Describe cyclic GMP to GMP
A
- GMP phosphodiesterase breaks down cyclic GMP to GMP
- decrease in concentration of cylic GMP reduces cyclic GMP bounds to cation channels, they close
- closed channels decrease NA+ influx into cytosol, slow neurotransmitter release and changing membrane potential/voltage channels
24
Q
Describe shutting down of GPCRs
A
- if active for a long time, GRK phosphorylates the receptor on the cytoplsamic side
- then arrestin binds, this recruits clathrin and the receptor is internalized by endocytosis
- the receptor will be degraded in lysosomes
25
Q
What does cross-talk mean between signaling pathways
A
- certain pathways described in this chapter can overlap each other and work across and in between each other in order to happen, can cycle around through all the steps
26
Q
Nanoparticles
A
- various types, such as: lipsome, albumin-based, micelle, polymer-based, and Gold
- examples above being used to deliver drugs in clinical trials
- have drugs and antibodies on outside; antibodies take out the “bad,” drugs treat cell
27
Q
What do radio waves do to iron oxide nanoparticles
A
- heat them up!
- example using insulin
- antibodies bring a nanoparticle to the body
- TRPVI is gate type structure in membrane that responds to heat by opening
- amino acid his tag binds particle to TRPVI
- opened channel brings more Ca2+ into cell, activates phosphatase, creates NFAT
- NFAT is a trasncription factor that will activate transcription of insulin, has P blocking/masking NLS
28
Q
Can the nanoparticles bind to cells expressing the TRPV1 channel with the his tag?
A
- Yes!
- nano particles binds to TRP channels on the surface of cells
29
Q
Can radio frequency cause an increase in Ca2+ in the cytoplasm?
A
Yes!
30
Q
Can the radio frequency cause NFAT to move in to the nucleus? Does the release of insulin depend on calcineurin?
A
- experiments in cell culture prove their idea will work in animal model
- NFAT moves into the nucleus when cells are exposed to radio frequency
- insulin release needs calcineurin activation
