Cell communication

1
Cell communication

• Receptor-ligand interactions- and what happens
  next

2
Why do cells communicate?

• In single-celled organisms
• Mating
• Quorum sensing
• In multicellular organisms

3
Overview of cell signaling

• A ligand binds to a receptor (reception)
• Whats a ligand? A small molecule (maybe a gas)
• Specific for the receptor
• The receptor triggers a signal transduction
• This causes a change in the cell (response)

4
What types of cell signaling occur in the body?
5
Where are the receptors?

• Inside the cell
• can bind hydrophobic ligands (often lipid)
• In the cell membrane
• Ligand is hydrophilic does not cross membrane
• Transmembrane protein is changed when ligand
  binds
• The receptor delivers the signal

6
Major types of receptors

• G protein-coupled (GPCR)
• Largest family many different pathways
• Receptor tyrosine kinase (RTK)
• Implicated in cancer
• One RTK can be linked to several pathways
• Ion channels
• Important in nervous system
• Ligand or voltage-gated

7
Types of receptors G protein-coupled
8
G protein-coupled receptors also regulate many
cell activities

• Many are involved in taste and smell also muscle
  responses
• Several hundred have been identified in humans
• G protein activation will cause an effector
  protein to be activated
• Enzyme
• Second messenger

9
Why different effects?

• Some G proteins stimulate signal transduction
• (Gs s stands for stimulatory)
• Some inhibit signal transduction (Gi)
• There are many different kinds of G proteins
• some have 3 subunits, some only one
• Distributed differently on different cells

10
RTK receptor tyrosine kinase
11
Superfamilies of receptors

• Have characteristic domains (functional parts
  of proteins)
• Ligand binding
• DNA binding
• Binding to regulatory molecules
• Activity is regulated within the cell
• Coactivators
• Coactivator levels may vary among tissues

12
Ion channels
13
Intracellular receptors for steroid ligands

• Receptor is in cytoplasm or nucleus
• Complex acts as transcription factor

14
Signal gets passed onto other molecules- then
what?

• It depends on the second-messenger pathway
  (signal transduction)

15
Why pathways?

• Amplification
• Fine regulation
• Phosphorylation and dephosphorylation
• Activates or deactivates proteins (enzymes)
• Kinases add phosphate groups
• Phosphatases remove them
• Serine/threonine
• Tyrosine
• Have OH groups and can react with phosphate

16
What is a second messenger?

• Effector proteins are often membrane-bound
• Second messenger can move through cell
• Most common examples of effector proteins
• Adenylyl cyclase
• Phospholipase C
• Can produce many types of second messengers
  (precursors are already in cell activated
  effector proteins change them)

17
cAMP signaling

• cAMP is quickly inactivated by phospho-diesterase
• Primary target of cAMP is protein kinase A (PKA)
• PKA has 4 subunits 2 regulatory, 2 catalytic
• cAMP binds to regulatory subunits
• catalytic subunits now detach and areactivated

18
What does this second-messenger system do?

• Some effects of cAMP (cell-specific)
• In skeletal muscle and liver?glycogenolysis
• Cardiac muscle- strengthens muscle contraction
• Smooth muscle- inhibits contraction
• Intestinal epithelium- movement of salt and water
  into gut

19
Calcium can be a second messenger, too
20
Calcium ions are associated with Neurotransmitte
rs Growth factors Some hormones Increase in
cytoplasmic concentration of calcium contributes
to Muscle cell contraction Neurotransmitter
release Antibody production Insulin
secretion Among others
21
Both G-protein and tyrosine kinase pathways can
utilize calcium as a second messenger Calcium
concentrations in cytoplasm are normally very
low Where does the calcium come from? from the
extracellular environment from the ER (calcium
is exported by calcium pumps within cell, to
keep internal calcium levels low)
22
(No Transcript)
23
Increasing efficiency and specificity

• Specificity of signaling- can be flexible!

• Scaffolding proteins

24
What is all this for? Transcription or
intracellular activity

• Nuclear (transcription)

• Cytoplasmic (enzymes)

25
Outcomes of cell signaling

• Enzyme activation
• Amplification
• Transcription and translation of specific genes
• Inhibition, in some cases

26
How do cells die naturally? Apoptosis (and its
genetic)

• Ced product is a caspase (protease)
• Signal may be external or internal
• Affect development and degeneration
• Is cell formation continuous throughout life?

27
Summary

• External signals, cell responses
• Can be local or distant
• Steps are reception, transduction, response
• Apoptosis is programmed cell death
• Lack of regulation can lead to disease