Chapter 5
Detection of Extracellular signals: the role of receptors
Objectives
• What are the main types of receptors• How to those receptors function in general• Why is ligand binding important• How do we measure ligand binding
Role of the Receptor
• Specificity, only one signal detected• High affinity, usually low concentrations 10-8 M• Must propagate message• Must turn off
Types of Receptors - G-protein Coupled Receptors
Gγ
Gβ Gα
Signal propagation
Signal propagation
Extracellular
Intracellular
–P P–
Types of Receptors – Enzyme Activity
Extracellular
Intracellular
Types of Receptors – Ligand Gated Channel
Extracellular
Intracellular
acetylcholine
sodium
GCPR
β2 Adrenergic Receptor
GPCR
• 7 Transmembrane helices• Signal through heterotrimeric G-proteins or
associated proteins• Mediate signaling for hormones,
neuropeptides, light, smell, and taste• Can involve phosphorylation
Ligand Gated Receptors
• Usually 5 membrane helices• Create a channel for ions• Rapid open / close• Function in neuronal
signaling
Enzyme Receptors
• Largest Group Receptor Tyrosine Kinases– Autophosphorylation– Dimers to be active
• Some Receptors phosphorylate other proteins
Intracellular Receptors
NPC
Hsp56
Hsp70
Hsp90
PromotorDNA
Nucleus
Cytosol
Extracellular
Ligand binding to Receptors
• Agonist – ligand that binds and activates a receptor
• Antagonist – ligand that binds receptor but does not activate it
• Constitutively Active – a receptor that is active in the absence of ligand
• Consider Ligand/Receptor binding as very similar to Ligand/Protein binding
Ligand binding to Receptors
Equations:
Ligand binding to Receptors
• How to measure [LR]– Fluorescence labeling
• Hard to quantify
– Radioisotope• 131I, 125I, 3H
– Influences• Time, pH, temperature, other ligands present…
Ligand binding to Receptors
• How much ligand binds nonspecifically– Compete with
unlabeled ligand– Subtract
• Kd
Total binding
Specific binding
Nonspecific binding
Scatchard Plot
Plot: vs
Scatchard Plots
Receptor Sensitivity
• Receptor Density– More receptors = better chance of detection– Less receptors = desensitization
• Clathrin coated vesicles and endocytosis
• Refractory Response– Homologous desensitization– Heterologous desensitization
Homologous desensitization
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