Signal Transduction Flashcards
How can cells communicate over large distances
Cells communicate via external signals (NT, hormones, chemical messengers, stimuli)
How are extracellular signals converted to intracellular events
Signal transduction
Via membrane receptors that cause response to activate second messengers that cause response
Where do intracellular messengers act
On target- ion channel, enzyme, cytoskeleton protein
3 kinds of signal transduction
Autocrine- act on self
Paracrine- act close by
Endocrine- act far away (go through blood stream)
Is ligand gated ion channel direct or indirect
Both
Ex. GPCR- AC- CAMP
Structure of ligand gated ion channels
Heteromeric
5 subunits each with 4 transmembrane spanning helices
- solved by x ray crystallography
Gating of ionotropic and metabotropic receptors
Ionotropic- ion channels- direct gating
Metabotropic- GPCRs- indirect gating
-most NTs have an ionotropic and metabotropic receptor (allowing for fast and slow responses from the same NT)
What two things can open GABA channels? What do GABA channels do
GABA and ethyl alcohol- NS depressant
- open Cl channels that will inhibit nerve transmission (reduce neural excitability)
Explain metabotropic receptor response? Also how many transmembrane helices
7 TM spanning helices
- extracellular ligand activate G protein that activates intracellular response or pathway
Structure of MAChR
7 TM helices
Central aqueous pocket containing ligand binding site
Intracellular G protein site
- diff subtypes, different G protein, diff functions
- M1-M5
What subunits in G protein
Alpha, gamma, beta (trimer)
Which subunit of G protein binds GTP
Alpha
What happens when the G protein is activated
Exchanges GDP for GTP bound state
Which G protein subunits can activate intracellular pathways
Alpha and beta-gamma together
What does alpha subunit of G protein activate
Effector protein
- activation leads to secondary messenger actions
What do a large amount of pharmacological drugs target
GPCRs (1/3)
Most studied GPCR
Rhodopsin
What are opsins and what do they mediate
Light activated GPCRs that mediate vision
Explain G protein activation and the contributing components
- ligand binds to and activates GPCR
- receptor interactions with G protein promotes a conformational change and the exchange of GDP for GTP
- GEF: guanine exchange factor facilitates dissociation of GDP and binding of GTP
- G protein dissociates from receptor (note: GTP state is active form)
- alpha-GTP and beta-gamma subunits dissociate
- alpha binds to effector
- beta-gamma can also interact with an effector
- RGS: regulator of G protein signaling. Facilitates hydrolysis and makes sure G protein was hydrolyzed to turn off activation
- alpha catalyzed hydrolysis of GTP to GDP inactivates alpha and promotes reassembly of trimer
Explain AC effector response and what G proteins stimulate this
Adenylyl cyclase activated in response to A or NA binding to B1 adrenergic receptors
Gs stimulates AC
GI inhibits AC
AC catalyses the conversion of ATP to cAMP
cAMP diffuses through cytosol to activate PKA
PKA phosphorylates
What activity does cAMP increase related to the heart
cAMP up regulates activity of voltage gated HCN channels causing HR to increase
What is Gt
Transducin
- G protein found in the retina
Explain light photo activating rhodopsin pathway
Light activates rhodopsin
Gt- transducin activates PDE- phosphodiesterase (effector)
PDE decrease cGMP (cGMP -> GMP), closes CNG channels that are normally open in the dark. This hyperpolarizes the cell and reduces glutamate release
ACh binds to M1 Gq pathway
Gq acts on phospholipase C (effector)
PLC cleaves PIP2 into DAG and IP3
DAG stays in plasma membrane
IP3 diffuse through cytosol and signals release of Ca from ER
Causes smooth muscle contraction and bronchoconstriction
How are signals amplified
1 NT can activate multiple GPCR
G protein alpha subunit can activate multiple effectors (ex. many AC)
Can generate multiple products (many cAMPs)
Activate many molecules (PKA)
Result is multiplied (kinase can phosphorylate many K channels)
