Flashcards in Biological Signalling: General + Types of Signal Transducers Deck (43)
What are the 4 Characteristics of Signal Transduction Pathways:
1. Specificity and Sensitivity
3. Desensitization and Adaptation
Signal transduction: Specificity
signal molecule fits the binding site on its complementary receptor
other signals do not fit
Increased specificity = ____ binding = ___ Kd
Additional features to increase specificity in cells?
- specific receptors depending onthe cell
Signal transduction: sensitivity: 3 factors
- high affinity of receptors for signal molecules
- cooperativity in ligand receptor interaction
- amplification of signal by enzyme cascades
What does a high affinity of receptors mean in terms of concentration of ligands needed and activation response?
- high affinity for receptors to bind means
- low concentration of ligand necessary to elicit a large activation response
Signal transduction: Amplification
- enzymes activate enzymes
- number of affected molecules increases geometrically in an enzyme cascade
Signal transduction: Desensitization / Adaptation
- receptor activation triggers feedback circuit
- that shuts off receptor or removes from cell surface
Protein kinases that phosphorylate and increase downstream protein kinases (kinase cascade) is an example of which signal transduction characteristic?
How are kinase cascades decreased?
protein phosphorylase removes phosphate
this shuts down the kinase cascade until stimulus reaches below a threshold
Signal Transduction: Integration
- two signals have opposite effects on metabolic characteristic
- regulatory net outcome (input from both receptors) elicits the response
- unified response appropriate to needs of organism
Types of signal transductors:
- G protein coupled receptor
- receptor tyrosine kinase
- receptor guanylyl cyclase
- gated ion channel
- adhesion receptor
- nuclear receptor
G protein coupled receptor
- ligand binds receptor
- activates GTP binding protein
- regulates enzyme that generates secondary messenger
i.e. adrenaline receptor -> PKA
Receptor tyrosine kinase
- ligand binding activates tyrosine kinase
- i.e. insulin receptor
Gated ion channel
- open/close channels in response to concentration of signal ligand or membrane potential
i.e. Ach receptor
Two types of neurotransmitters for ionotropic receptors:
- biogenic amines
- amino acids
Which biogenic amines give a positive effect to nerve transmission?
- acetyl choline
- nicotinic receptors
- muscarini c receptors (M1-5)
What is Ach and what does it do?
- main neurotransmitter for nerve-muscle (voluntary); CNS; parasympathetic (involuntary)
What do nicotinic receptors do?
- triggers Na+ and Ca+ inflow (down gradient)
- activation [nicotine]
Which biogenic amines give a negative effect to nerve transmission?
- Gamma-aminobutyric acid (GABA)
- a major inhibitory NT in the CNS
What do GABA receptors do?
- inhibit NT in CNS
- triggers influx of Cl- (recall Cl- is high outside)
- hyperpolarizing (cuz too negative inside)
- inactivation [tranquilizers, alcohol, barbiturates]
Which amino acid neurotransmitters for ionotropic receptors give a positive effect?
- AMPA, Kainate, NMDA, delta receptors
What does glutamate do?
major NT in CNS
What do the AMPA, Kainate, NMDA, delta receptors do?
- triggers Na+ and Ca2+ influx
- involved in learning, memory, plasticity
Which amino acid neurotransmitters for ionotropic receptors give a negative effect?
What doe glycine receptors trigger?
- Cl- influx
Nicotinic acetylcholine receptor (AchR) - how do electrical signals travel
- passage of electrical signal from motor neuron to muscle fiber at neuromuscular junction
How is acetylcholine released and bound?
- released by motor neuron
- diffuse to plasma membrane of myocyte
- binds AchR
How is a muscle contraction triggered?
- Ach bound
- conformational change in AchR = open
- inward movement of Ca2+ and Na+
- triggers muscle contraction
In the first step of neural transmission, what does Ach cause?
- ach opens ach receptors (ligand gated Na+ Ca2+ channel)
- Na+ flows in (down gradient)
- small depolarization (-70 to -40mV)
Explain the repolarizing dip.
- K+ channels repolarize causes the drop in membrane potential
- the K+ flow out of the cell (down gradient) -75mV
- the K+ channels inactivate -60mV
What is the wave that travels along the axon?
- wave of depolarization and repolarization
What is the process that releases neurotransmitters into the synaptic cleft?
- which then causes the small depolarization...
How many subunits does AchR have?
How many helices does each subunit of AchR have?
AchR is a ____ gated channel
ligand gated (Ach)
Where are the M2 helices located?
The M2 helix in the 5 subdomains face the interior of the channel.
What is the facing of the M2 helices when the channel is closed?
face the interior of the channel
What is the unique property of M2
hydrophobic leucine on one side, but has polar residues on other side
What triggers the twist?
2 Acetylcholines bind
What twists when Ach binds?
the 5 subunits each twist
- "Quaternary Twist" to open the pore
What happens when the subunits twist?
the M2 helices expose the negative groups
- small, polar residues line the channel
- allows anything that is positive to flow in - no selectivity for Na+ Ca2+ K+
- depolarize (Na+ and Ca2+ can flow in)