receptors and signal transduction

types of receptors and examples of each

receptors without endogenous ligand (non real): transporters, channels, enzymes, structural proteins, nucleic acid
receptors for endogenous regulatory ligands (real): receptors for hormones, neurotransmitters, growth factors, and cytokines

2 important properties of signal transducing receptors

1. sensing the ligand

2. transmitting the message

transmembrane receptors

Integral membrane proteins possessing an extracellular binding domain and an intracellular signaling domain

intracellular receptors

Located within the cytosol or nucleus; require lipophilic (lipid-soluble) ligands to cross the cell membrane

isoforms

Receptors frequently exist as multiple structural isoforms that differ in signaling pathways, providing cellular and tissue-level regulatory flexibility

ion channel structure/shape, function, differences, and speed

Direct channel opening, allowing rapid flux of ions across the cell membrane
Voltage-Gated Ion Channels: activated by changes in the transmembrane electrical potential gradient
Ligand-Gated Ion Channels: activated directly by agonist binding to an extracellular domain
Speed: fast

G protein coupled receptors structure/shape, function, protein structures, cycle, and 2nd messengers

7 transmembrane a helical domains with N and C terminals
Ligand - G protein activation - heterotrimeric G protein activation - effector - 2nd messenger - cellular response
Resting state: ABY intact with GDP
Activated state: GTP replaces GDP on a, BY
Regulatory cycle: resting state - agonist binding - GTP GDP exchange - dissociation/effector activation - GTP hydrolysis/ reassembly
2nd messengers: cAMP, IP3, DAG, Ca2+
Speed: seconds to minutes

Gs

stimulatory, activates adenylyl cyclase = increase cAMP

Gi

inhibitory, inhibits adenylyl cyclase = decrease cAMP

Gq

activates phospholipase C = increase IP3, DAG, and Ca2+

Enzyme linked receptors structure/shape, function, types by enzymatic domain location, and speed

single transmembrane spanning protein, many form dimmers upon activation
transduce an extracellular ligand binding interaction into an intercellular action through the activation of a linked enzymatic domain
The enzymatic domain part of receptor itself: receptor tyrosine kinase
The enzymatic domain part of cytosolic protein that is recruited to the receptor in response to receptor activation: JAK STAT receptor pathway
Speed is slow

intracellular receptors structure/shape/location and functions

a lipid soluble ligand/drug can cross the membrane to act on an intracellular receptor
Mostly found in nucleus/cytosol
Ligand binding induces gene transcription

receptor desensitization and its mechanisms

receptors are subject to feedback regulatory controls
desensitization often follows continued stimulation with agonists (diminishing effects over time)
mechanisms: phosphorylation, internalization, alteration in rate of synthesis

homologous desensitization

adding an agonist for receptor A, desensitizes receptor A

heterologous desensitization

adding an agonist for receptor A, desensitizes receptor B