Transcript The Structure of a G-protein –linked Receptor

Chapter 11
Cell Communication
Cell Signaling Evolved early in
the History of Life
Communication between
mating yeast cells.
Yeast cells use chemical
signaling
Induced changes lead to
fusion.
The resulting a/a cell is
diploid.
Local Chemical Signaling
Paracrine
Secreting cell acts on nearby target cell by
discharging molecules into the extracellular fluid
Synaptic
Nerve cell releases neurotransmitter into synapses
Distant Cell Communication
Hormones signal target cells at much greater
distances.
Secreted into the body fluids, they reach all parts of
the body.
Only specific target cells are recognized and
respond
Major Glands and their
Hormones
Growth Hormone
Thyroxine
Epinephrine (adrenaline)
Insulin and Glucagon
Testosterone
Estrogen
Local and Distant Cell Communication In Animals.
Cells also communicate by direct
contact.
1. Cell Junctions
Signaling substances dissolved in the cell can pass
freely from one cell to another
2. Direct Contact
Through molecules on the surface of the cell
(embryonic development and the immune system)
Communication
by Direct
Contact with
Cells.
The Three Stages of Cell
Signaling
For a chemical signal to elicit a specific
response, the target cell must possess a
signaling system for the signal.
1. Reception
2. Transduction
3. Response
Overview of Cell Signaling.
Reception – signal (ligand) binds to a
specific cell surface protein.
Transduction – binding results in
conformation change of receptor. This
initiates transduction (one or many
steps)
Response – almost any cellular activity
• Many signal molecules cannot pass freely
through the plasma membrane
• Receptors are located on the plasma
membrane
• These families are called:
- G-protein linked receptors
- tyrosine kinase receptors
- ion channel receptors
The Structure of a G-protein –linked Receptor.
The Functioning of
a G-Protein
Linked- Receptor
(e.g. epinephrine
receptor).
• G-proteins bind guanine nucleotides
• GDP – inactive state, GTP – active state
• Signal binding changes receptor
conformation
• Interacts with G-protein
• G-protein binds GTP
• Activated G-protein binds to another
protein (enzyme)
• Activation of subsequent target.
• Activation state is temporary
• Critical metabolic and developmental
processes
• Defects in G-protein signaling form the
bases of many human disease states.
• Cholera, whooping cough and botulism,
due to toxins that interfere with G-protein
function.
The Structure and
Function of a
Tyrosine Kinase
Receptor.
Tyrosine Kinase Receptors
• Extracellular ligand-binding domain.
• Cytosolic domain with tyrosine kinase (tk)
enzyme activity.
Ligand binding causes dimerization.
Activates endogenous tk activity.
Transfer of PO4 from ATP to tyrosine – autophosphorylation.
Interaction with other cellular proteins, resulting in activation of
relay proteins – many responses
Protein phosphatase terminates the signal process
A ligand-gated ion-channel
receptor.
(important in nervous system)
Overview Animation
Reception 11.2
http://bcs.whfreeman.com/thelifewire/content/chp15/15020.html
http://www.wiley.com/college/fob/anim/
http://www.youtube.com/watch?v=3nODx3cT1RU
Not All Signal Receptors Are
Located on the Plasma Membrane
• Some receptors are proteins located in the
cytoplasm or nucleus
• The signal molecules for these receptors must
be able to pass through the plasma membrane
• Examples of signals that bind to intracellular
receptors are: Nitric oxide, steroid and thyroid
hormones
Pathways Relay Signals From
Receptors to Cellular Responses
• The signal molecule is not physically
passed along the transduction pathway.
• The information is passed along.
• It is converted or transduced at each
step.
Protein Phosphorylation
• Transfer of a phosphate group
• From ATP to a protein substrate
(serine or threonine residues)
• Catalyzed by protein kinases
• Regulates functional activity of
proteins
• 1% of our genes code for protein
kinases
• Effects of protein kinases are
reversed by protein phosphatases
A Phosphorylation
Cascade.
Cyclic AMP (cAMP)
•Some signaling systems rely on small non-protein water
soluble molecules or ions.
•These are called second messengers.
•Examples: cAMP
cAMP as a
Second
Messenger.
Amplification
Cytoplasmic
Response to
a Signal.
Cellular Responses
Signaling can effect the function or
activity of proteins that carry out various
processes such as:
– Rearrangement of the cytoskeleton
– Opening or closing of an ion channel
– Serve at key points in metabolic pathways
– Modulation of gene expression in the
nucleus
Nuclear
Response
to a Signal.
Signal Specificity
• A particular signal can bind to different cell types
and result in different responses in each cell
• Example, epinephrine action
• In liver cells – glycogen breakdown
• In cardiac muscle cells – contraction