Cellular Communication

The Cellular Internet

Overview: The Cellular Internet
 Cell-to-cell communication is essential for
multicellular life
 Life shares universal mechanisms of cellular
regulation involving the same small set of
cell-signaling mechanisms.
 Chemical signals, electromagnetic signals,
and mechanical signals.
External signals are converted into
responses within the cell
 We learn a great deal from the microbial world.

 The yeast Saccharomyces cerevisiae, the

yeast of bread, wine, and beer, identifies its
mates by chemical signaling.

 Many cells in our body respond to chemical

signals using the same pathways as yeast.
  factor
Receptor

1
Exchange a 
of mating
factors
a factor
Yeast cell, Yeast cell,
mating type a mating type 

2 Mating a 

3 New a/ a/

cell
Evolution of Cell Signaling
 Signal-transduction pathway

 Pathway similarities suggest that ancestral

signaling molecules evolved in prokaryotes and
have since been adopted by eukaryotes
Local and Long-Distance
Signaling
 Chemical messages

 Cell Junctions

 Local signaling
 Localmessengers
 Long Distance Signaling
 Hormones- vary in size and type
 Ethylene (C2H4), Insulin (C256H381N65O79S6)
Fig. 11-4
Plasma membranes

Gap junctions Plasmodesmata

between animal cells between plant cells

(a) Cell junctions

(b) Cell-cell recognition

 Local signaling
Long-distance signaling
Hormone travels
Electrical signal in bloodstream
Local regulator along nerve cell to target cells
diffuses through triggers release of
extracellular fluid neurotransmitter
Endocrine cell
Neurotransmitter Blood
diffuses across vessel
Secreting
cell synapse

Target cell
is stimulated

Target
Target cell cell

Paracrine signaling Synaptic signaling

Hormonal signaling
The Three Stages of Cell
Signaling: A Preview
 Earl W. Sutherland discovered how the
hormone epinephrine acts on cells
 There are three steps:
 Reception

 Transduction

 Response
Sutherlands research
 Sutherland’s research team discovered that
epinephrine activated a enzyme, glycogen
phosphorylase.
 However, epinephrine did not activate the
phosphorylase directly but could only act on
intact cells.
 Therefore, there must be an intermediate step
or steps occurring inside the cell.
 Also, the plasma membrane must be involved
in transmitting the epinephrine signal.
The 3 steps
 Reception: A signal molecule binds to a
receptor protein, causing it to change shape

 Occurs between ligand and receptor

protein.

 Based on shape

 Very specific

 Most signal receptors are plasma membrane

proteins
 Intracellular Receptors
 Some receptor proteins are intracellular
 Small or hydrophobic chemical messengers can
readily cross the membrane and activate
receptors
 Examples of hydrophobic messengers are the
steroid and thyroid hormones (testosterone)
 An activated hormone-receptor complex can act
as a transcription factor, turning on specific
genes
Fig. 11-8-5
Hormone EXTRACELLULAR
(testosterone) FLUID

Plasma
membrane
Receptor
protein
Hormone-
receptor
complex

DNA

mRNA

NUCLEUS New protein

CYTOPLASM
 Receptors in the Plasma Membrane

 Water soluble bind here

 There are three main types of membrane
receptors:
 G-protein-linked receptors
 Receptor tyrosine kinases
 Ion channel receptors
G-Protein Guanine nucleotide-binding
proteins
 A G protein-coupled receptor is a plasma
membrane receptor that works with the help
of a G protein
 The receptor consists of seven alpha helices
spanning the membrane.
 Activated by many ligands and has many
functions
 The G protein acts as an on-off switch.
 If GDP is bound, the G protein is inactive.
 If GTP is bound, the G protein is active.
 Signal-binding site

Segment that
interacts with
G proteins
G-protein-linked receptor
The G protein can also act as a GTPase enzyme and
This change turns the G protein off.
The whole system can be shut down quickly when the
extracellular signal molecule is no longer present
G-protein
 G-protein receptor systems are extremely
widespread and diverse in their functions.
 play an important role during embryonic
development and sensory systems.
 350 know genes in our genome code for G
protein
 Half of all medications act on it
 Tyrosine kinases
 Attach phosphates to tyrosines on the cytoplasmic
side

 90 know genes

 can trigger multiple pathways at once

 Gleevec and anti-cancer drug inhibits it

Inactive TKR
 Ligand-gated ion channels

 Signal binds and opens the channels

allowing ions such as Na+ or Ca2+,
through a channel in the receptor
 Ions
Signal
molecule
(ligand)

Plasma
Ligand-gated membrane
ion channel receptor

Gate open

Cellular
response

Gate closed
Transduction

 Transduction usually involves multiple

steps
 Multistep pathways
 1. Can amplify a signal: A few molecules
can produce a large cellular response
 2. Multistep pathways provide more
opportunities for coordination and
regulation
Signal Transduction Pathways
 Mostly proteins

 Act like passing a baton in track!

 At each step the signal is transduced into

a different form
Protein Phosphorylation and
Dephosphorylation
 (Protein kinase) is a widespread cellular
mechanism for regulating protein activity.
 Add phosphates to proteins

 Phosphatase
 remove the phosphates

 This phosphorylation and

dephosphorylation system acts as a
molecular switch, turning activities on and
off
Protein Kinases
 A single cell may have hundreds of
different protein kinases, each specific for
a different substrate protein.
 Fully 1% of our genes code for protein
kinases.
 Small Molecules and Ions as
Second Messengers
 Second messengers are small, nonprotein,
water-soluble molecules or ions

 Second messengers participate in pathways

initiated by G-protein-linked receptors and
receptor tyrosine kinases

 2 of the most important are cyclic AMP and Ca2+.

Cyclic AMP

 One of the most widely used second

messengers

 Adenylyl cyclase which converts ATP to

cAMP.
 cAMP is short-lived
 phosphodiesterase converts it to AMP
cAMP
 cAMP
 cAMP usually activates protein kinase A,
which phosphorylates various other proteins

 Further regulation of cell metabolism is

provided by G-protein systems that inhibit
adenylyl cyclase
Fig. 11-11
First messenger

Adenylyl
G protein cyclase

G protein-coupled GTP
receptor

ATP
Second
cAMP messenger

Protein
kinase A

Cellular responses
Ex.
 Certain microbes cause disease by disrupting
the G-protein signaling pathways.
 The cholera bacterium, Vibrio cholerae,
colonizes the the small intestine and produces
a toxin that modifies a G protein that regulates
salt and water secretion.
 The modified G protein is stuck in its active
form, continuously stimulating productions of
cAMP.
 This causes the intestinal cells to secrete large
amounts of water and salts into the intestines,
leading to profuse diarrhea and death if
untreated.
 Calcium ions and Inositol
Triphosphate (IP3)
 Calcium ions (Ca2+) act as a second
messenger in many pathways

 Cells can regulate its concentration

 Cells use Ca2+ as a second messenger in

both G-protein pathways and tyrosine-
kinase pathways.
 DAG and IP3
 A signal relayed by a signal transduction pathway
may trigger an increase in calcium in the cytosol
 Pathways leading to the release of calcium involve
inositol triphosphate (IP3) and diacylglycerol (DAG)
as second messengers
 Both molecules are produced by cleavage of certain
phospholipids in the plasma membrane.
 DAG and IP3 are created when a phospholipase
cleaves a membrane phospholipid PIP2.
 Phospholipase may be activated by a G protein or a
tyrosine-kinase receptor.
 IP3 activates a gated-calcium channel, releasing Ca 2+.
 Cont..
 Calcium ions may activate a signal-transduction
pathway directly.

 Alternatively, Ca2+ binds to the protein

calmodulin.
 This protein is present at high levels in
eukaryotes.

 Calmodulin binds to other proteins, either

activating or inactivating them.
 Response: Cell signaling leads to regulation
of cytoplasmic activities or transcription
 Ultimately, a signal transduction pathway leads to
regulation of one or more cellular activities
 The response may occur in the cytoplasm or may
involve action in the nucleus
 Many signaling pathways regulate the synthesis of
enzymes or other proteins, usually by turning
genes on or off in the nucleus
 The final activated molecule may function as a
transcription factor
EX.
The Specificity of Cell Signaling
 Different kinds of cells have different collections
of proteins
 These differences in proteins give each kind of
cell specificity in detecting and responding to
signals
 The response of a cell to a signal depends on
the cell’s particular collection of proteins
 For example, epinephrine triggers liver or
striated muscle cells to break down glycogen,
but cardiac muscle cells are stimulated to
contract, leading to a rapid heartbeat.
Fig. 11-17a

Signaling
molecule

Receptor

Relay
molecules

Response 1 Response 2 Response 3

Cell A. Pathway leads Cell B. Pathway branches,

to a single response. leading to two responses.
Fig. 11-17b

Activation
or inhibition

Response 4 Response 5

Cell C. Cross-talk occurs Cell D. Different receptor

between two pathways. leads to a different response.
Signaling Efficiency: Scaffolding
Proteins and Signaling Complexes
 Scaffolding proteins are large relay proteins
to which other relay proteins are attached
 Scaffolding proteins can increase the signal
transduction efficiency by grouping
Apoptosis
 Programmed cell death!

 Important in immunity, formation of the body,

Cancer prevention, Immunocompetency etc
etc
Fig. 11-20a

Ced-9
protein (active)
inhibits Ced-4
activity

Mitochondrion

Ced-4 Ced-3
Receptor
for death-
Inactive proteins
signaling
molecule

(a) No death signal

Fig. 11-20b

Ced-9 Cell
(inactive) forms
blebs

Death-
signaling
molecule

Active Active
Other
Ced-4 Ced-3
proteases

Nucleases
Activation
cascade

(b) Death signal