signalling at cell surface l.
Download
Skip this Video
Loading SlideShow in 5 Seconds..
Signalling at Cell Surface PowerPoint Presentation
Download Presentation
Signalling at Cell Surface

Loading in 2 Seconds...

play fullscreen
1 / 55

Signalling at Cell Surface - PowerPoint PPT Presentation


  • 96 Views
  • Uploaded on

Signalling at Cell Surface. 2 April 2007. Receptors. Classification of receptors. Intracellular receptors (for lipid soluble messengers) function in the nucleus as transcription factors to alter the rate of transcription of particular genes.

loader
I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
capcha
Download Presentation

PowerPoint Slideshow about 'Signalling at Cell Surface' - miracle


An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript
slide3

Classification of receptors

  • Intracellular receptors (for lipid soluble messengers)
      • function in the nucleus as transcription factors to alter the rate of transcription of particular genes.
  • Plasma membrane receptors (for lipid insoluble messengers)
      • Receptors function as ion channels
      • receptors function as enzymes or are closely associated with cytoplasmic enzymes
      • receptors that activate G proteins which in turn act upon effector proteins, either ion channels or enzymes, in the plasma membrane.
slide4

Cell Surface Receptors

  • May work both fast and slow
  • Always use “second messengers”
cell surface receptors belong to four major classes
Cell-Surface Receptors Belong to Four Major Classes
  • G proteincoupled receptors : epinephrine, serotonin, and glucagon.
  • Ion-channel receptors: acetylcholine receptor at the nerve-muscle junction.
  • Tyrosine kinase linked receptors: cytokines, interferons, and human growth factor.
  • Receptors with intrinsic enzymatic activity
receptor ion channels
RECEPTORION CHANNELS
  • multi-subunit, transmembrane protein complexes
  • complex is both the receptor and ion channel
  • stimuli: chemical, stretch or voltage
  • stimulus induces conformational change to open or close ion channel
  • two types:

1) ligand-gated ion channel

2) voltage-gated ion channel

slide9

LIGAND-GATED ION CHANNELS

  • chemical stimuli bind to receptor and open or close ion channel
  • stimuli can be extracellular or intracellular
    • EXTRACELLULAR STIMULI: (neurotransmitters)
    • e.g. acetylcholine, dopamine, GABA, glutamate
    • INTRACELLULAR STIMULI: (second messengers)
    • e.g. IP3, cAMP, cGMP, Ca2+
slide10

LIGAND-GATED ION CHANNEL AT THE SYNAPSE

  • occurs at gap (synaspe) between nerve and target cell
  • acetylcholine (ACh) released into synapse
  • ACh binds to ion channel on target cell, opens channel, influx of Na+
  • enzyme acetylcholinesterase released into synapse to breakdown ACh
slide11

ACETYLCHOLINE ANTAGONISTS

  • very potent neurotoxins
  • bind to receptor and prevent opening of Na+ channel
    • e.g. cobratoxin from Indian cobra
    • atropine from deadly nightshade
    • S. American arrow poison (curare) - very fast acting so shot animals don’t run too far
slide12

VOLTAGE GATED ION CHANNELS

  • ion channel undergoes conformational change folllowing electrical stimulus
  • this “depolarization” opens the channel
    • leads to flow of Na+ into cell
    • constitutes an “action potential”
  • channel recloses
slide13
Signaling pathways downstream from G protein coupled receptors (GPCRs) and receptor tyrosine kinases (RTKs)
intracellular proteins
Intracellular proteins
  • Two groups of evolutionary conserved proteins function in signal transduction
  • 1. GTPase switch proteins
    • Conversion from GDP bound inactive state to GTP-bound active state is mediated by guanine nucleotide exchange factors (GEFs)
    • Intrinsic GTPase activity hydrolyzes bound GTP to GDP + Pi
slide17
GTP hydrolysis is accelerated by GTPase accelerating protein (GAPs)
  • Two classes of GTPase switch proteins:
    • Trimeric (large) G proteins
      • Directly bind to receptors
    • Monomeric (small) G proteins
      • Linked to receptors via adapter proteins and GEFs
slide20
2. Protein kinases and phosphatases
    • Human genome encodes 500 PKs and 100 PPs
    • Two types of PK
      • Those that P* OH group on Tyr residue
      • Those that P* OH group on Ser or Thr residues
    • PK is activated
      • By other kinases
      • By direct binding to other proteins
      • By second messengers
regulation of signaling
Regulation of signaling
  • External signal decreases
    • Degradation of second mesenger
  • Desensitization to prolonged signaling
    • Receptor endocytosis
  • Modulation of receptor activity
    • Phosphorylation
    • Binding to other proteins
g protein coupled receptors
G Protein-Coupled Receptors
  • A very large family of receptors coupled to trimeric G proteins
  • Activate or inhibit adenylyl cyclase
  • All have seven membrane spanning region
  • Ligands include:
    • Hormones, neurotransmitters, light activated receptors (rhodopsins), thousands of odorant receptors
slide25
Signal transducing G protein has 3 subunits
    • G, Gß and G
  • G is the GTPase switch protein and modulates the activity of an effector protein
  • Effector proteins are either membrane bound ion channels or enzymes generating second messengers
slide33
GPCR-mediated dissociation of trimeric G proteins has been demonstarted in fluorescence energy transfer experiments
slide37

The activation/deactivation cycle of G proteins

Agonist-receptor

complex

+

GTP

GDP

GTP

GDP

Inactive

effector

Active

effector

Pi

Active

effector

GDP

GTP

slide38

G proteins can be linked to:

  • adenylate cyclase
    • produces cyclic AMP (cAMP)
  • guanyl cyclase
    • produces cyclic GMP (cGMP)
  • phospholipase C
    • produces inositol trisphosphate (IP3)
    • and diacyl glycerol (DAG)
  • ion channels
slide40

first

messenger

receptor

transducer

amplifier

second

messenger

slide41

Activity of bg subunits

  • Activation of K+ Channels
slide42

G-Protein-Activated Enzymes

  • Generate new molecules - “second messengers
epinephrine case
Epinephrine case
  • Mediates body’s response to stress, when all tissues need glucose and fatty acids to produce ATP
  • ß-adrenergic receptors
    • Heart muscle: contraction
    • Smooth muscle cells of intestine: relax
  • 2-adrenergic receptors
    • Smooth muscle cells of endothelium, skin, kidney and intestine: constrict
slide47
ß1 and ß2 adrenergic receptors are coupled to stimulatory G protein (Gs)
    • Actvates adenylyl cyclase
  • 1 adrenergic receptor is coupled to inhibitory G protein (Gi)
    • Inhibits adenylyl cyclase
  • 2 adrenergic receptor is coupled to Gq that activates another effector enzyme
slide48
Bacterial toxins
    • Vibrio cholera
      • Catalyzes chemical modification of Gs that prevents hydrolysis of GTP to GDP
        • Active state
    • Bordetella pertussis
      • Catalyzes chemical modification of Gi that prevents release of GDP
        • Inactive state
slide49
Critical domain of GPCR resides in C3 loop according to chimeric receptor expression experiments
slide55
Differential modulation of adenylyl cyclase
  • Different hormone-receptor complexes modulate the activity of the same effector molecule
    • In liver glucagon and epinephrine bind to different receptors but activate the same Gs: same metabolic responses