Cell Communication
Jan 17, 2016
Cell Communication
• Cell-to-cell communication is absolutely essential for multicellular organisms and is also important for many unicellular organisms
• Cells must communicate to coordinate their activities
Cell Communication
Biologists have discovered some universal mechanisms of cellular regulation, involving the same small set of cell-signaling mechanisms
The “Cellular Internet”
• External signals are converted into responses within the cell
Evolution of Cell Signaling
Yeast cells• Identify their mates by cell signaling
factorReceptor
Exchange of mating factors. Each cell type secretes a mating factor that binds to receptors on the other cell type.
1
Mating. Binding of the factors to receptors induces changes in the cells that lead to their fusion.
New a/ cell. The nucleus of the fused cell includes all the genes from the a and cells.
2
3
factorYeast cell,mating type a
Yeast cell,mating type
a/
a
a
Methods used by Cells to Communicate
Cell-Cell communication
Cell Signaling using chemical messengers
Plasma membranes
Plasmodesmatabetween plant cells
Gap junctionsbetween animal cells
Local regulator diffuses through extracellular fluid
Target cell
Secretoryvesicle
Electrical signalalong nerve celltriggers release ofneurotransmitter
Neurotransmitter diffuses acrosssynapse
Target cellis stimulated
Local signaling
1. Local signaling over short distances
2. Long distance signaling
• Cell-Cell Recognition
• Local regulators
Paracrine (growth factors)
Synaptic (neurotransmitters)
• Hormones
Cell-Cell Communication
Plasma membranes
Plasmodesmatabetween plant cells
Gap junctionsbetween animal cells
Figure 11.3 (a) Cell junctions. Both animals and plants have cell junctions that allow molecules to pass readily between adjacent cells without crossing plasma membranes.
Animal and plant cells
• Have cell junctions that directly connect the cytoplasm of adjacent cells
Cell-Cell Communication
Animal cells use gap junctions to send signals
• cells must be in direct contact
• protein channels connecting two adjoining cells
Gap junctionsbetween animal cells
Cell-Cell Communication
Plant cells use plasmodesmata to send signals
• cells must be in direct contact
• gaps in the cell wall connecting the two adjoining cells together
Plasmodesmata between plant cells
Local Signaling: Cell-Cell Recognition
In local signaling, animal cells may communicate via direct contact
• Membrane bound cell surface molecules
• Glycoproteins
• Glyolipids
(Cell-cell recognition. Two cells in an animal may communicate by interaction between molecules protruding from their surfaces.
Local Signaling: Local Regulators
In other cases, animal cells
• Communicate using local regulators
• Only work over a short distance
(a) Paracrine signaling. A secreting cell acts on nearby target cells by discharging molecules of a local regulator (a growth factor, for example) into the extracellular fluid.
(b) Synaptic signaling. A nerve cell releases neurotransmitter molecules into a synapse, stimulating the target cell.
Local regulator diffuses through extracellular fluid
Target cell
Secretoryvesicle
Electrical signalalong nerve celltriggers release ofneurotransmitter
Neurotransmitter diffuses acrosssynapse
Target cellis stimulated
Local signaling
Long-distance Signaling: Hormones
In long-distance signaling
• Both plants and animals use hormones
Hormone travelsin bloodstreamto target cells
(c) Hormonal signaling. Specialized endocrine cells secrete hormones into body fluids, often the blood. Hormones may reach virtually all body cells.
Long-distance signaling
Bloodvessel
Targetcell
Endocrine cell
Long-Distance Signaling
Nervous System in Animals Electrical signals through neurons
Endocrine System in Animals Uses hormones to transmit messages
over long distances
Plants also use hormones Some transported through vascular
system Others are released into the air
How do Cells Communicate?
Earl W. Sutherland
• Discovered how the hormone epinephrine acts on cells
How do Cells Communicate?
Sutherland suggested that cells receiving signals went through three processes
Reception
Transduction
Response
Called Signal transduction pathways
• Convert signals on a cell’s surface into cellular responses
• Are similar in microbes and mammals, suggesting an early origin
How do Cells Communicate?
The process must involve three stages
1. Reception - a chemical signal binds to a cellular protein, typically at the cell’s surface
2. Transduction - binding leads to a change in the receptor that triggers a series of changes along a signal-transduction pathway
3. Response - the transduced signal triggers a specific cellular response
Signal Transduction Animation
• http://media.pearsoncmg.com/bc/bc_campbell_biology_7/media/interactivemedia/activities/load.html?11&A
• http://www.wiley.com/legacy/college/boyer/0470003790/animations/signal_transduction/signal_transduction.htm
Signal molecules and Receptor Proteins
A cell targeted by a particular chemical signal has a receptor protein that recognizes the signal molecule
• recognition occurs when the signal binds to a specific site on the receptor because it is complementary in shape
When ligands (small molecules that bind specifically to a larger molecule) attach to the receptor protein, the receptor typically undergoes a change in shape
• this may activate the receptor so that it can interact with other molecules
Signal Molecules
• most signal molecules are water-soluble and too large to pass through the plasma membrane
• they influence cell activities by binding to receptor proteins on the plasma membrane
– binding leads to change in the shape of the receptor
– these trigger changes in the intracellular environment
There are three common types of membrane receptor proteins:
• G-protein coupled receptors• Receptor tyrosine-kinases• Ion channel receptors
1. ReceptionA signal molecule, a ligand, binds to a receptor
protein in a lock and key fashion, causing the receptor to change shape.
• Most receptor proteins are in the cell membrane but some are inside the cell.
G Protein- Coupled Receptor
• the receptor consists of seven alpha helices spanning the membrane
G protein-coupledreceptor
Plasmamembrane
Enzyme
G protein(inactive)
GDP
CYTOPLASM
Activatedenzyme
GTP
Cellular response
GDP
P
i
Activatedreceptor
GDP GTP
Signaling molecule
Inactiveenzyme
1 2
3 4
G-Protein Receptors
• effective signal molecules include yeast mating factors, epinephrine, other hormones, and neurotransmitters
Several human diseases are the results of activities, including bacterial infections, that interfere with G protein function
cholera
pertussis
botulism
Receptor tyrosine kinases
Signalmolecule
Signal-binding site
CYTOPLASM
Tyrosines
Signal moleculeHelix in the
Membrane
Tyr
TyrTyr
Tyr
Tyr
TyrTyr
TyrTyr
Tyr
Tyr
Tyr
Tyr
TyrTyr
Tyr
Tyr
Tyr Tyr
TyrTyr
Tyr
Tyr
Tyr
Tyr
TyrTyr
Tyr
Tyr
Tyr
DimerReceptor tyrosinekinase proteins(inactive monomers)
PP
PP
P
P Tyr
TyrTyr
Tyr
Tyr
TyrP
P
P
P
P
PCellularresponse 1
Inactiverelay proteins
Activatedrelay proteins
Cellularresponse 2
Activated tyrosine-kinase regions(unphosphorylateddimer)
Fully activated receptortyrosine-kinase(phosphorylateddimer)
6 ATP 6 ADP
Ligand-gated Ion Channels• Ligand-gated ion channels are
protein pores that open or close in response to a chemical signal
• this allows or blocks ion flow, such as Na+ or Ca2+
• binding by a ligand to the extracellular side changes the protein’s shape and opens the channel
• ion flow changes the concentration inside the cell
Signalingmolecule(ligand)
Gateclosed Ions
Ligand-gatedion channel receptor
Plasmamembrane
Gate open
Cellularresponse
Gate closed
1
2
3
Ion Channel Receptors
• Very important in the nervous system
• Signal triggers the opening of an ion channel– Depolarization– Triggered by
neurotransmitters
2. Transduction• Transduction: Cascades of molecular
interactions relay signals from receptors to target molecules in the cell
• Multistep pathways– Can amplify a signal (Amplifies the signal by
activating multiple copies of the next component in the pathway)
– Provide more opportunities for coordination and regulation
• At each step in a pathway, the signal is transduced into a different form, commonly a conformational change in a protein.
Signaling molecule
ReceptorActivated relaymolecule
Inactiveprotein kinase1 Active
proteinkinase1
Inactiveprotein kinase2
ATPADP Active
proteinkinase2
P
PPP
Inactiveprotein kinase3
ATPADP Active
proteinkinase3
P
PPP
i
ATPADP P
ActiveproteinPP
P i
Inactiveprotein
Cellularresponse
Phosphorylation cascade
i
Transduction:A Phosphorylation Cascade
Protein Phosphorylation and Dephosphorylation
Many signal pathways
• Include phosphorylation cascades
• In this process, a series of protein kinases add a phosphate to the next one in line, activating it
• Phosphatase enzymes then remove the phosphates
Signal molecule
Activeproteinkinase1
Activeproteinkinase2
Activeproteinkinase3
Inactiveprotein kinase1
Inactiveprotein kinase2
Inactiveprotein kinase3
Inactiveprotein
Activeprotein
Cellularresponse
Receptor
P
P
P
ATPADP
ADP
ADP
ATP
ATP
PP
PP
PP
Activated relaymolecule
i
Phosphorylation cascade
P
P
i
i
P
A phosphorylation cascade
A relay moleculeactivates protein kinase 1.1
2 Active protein kinase 1transfers a phosphate from ATPto an inactive molecule ofprotein kinase 2, thus activatingthis second kinase.
Active protein kinase 2then catalyzes the phos-phorylation (and activation) ofprotein kinase 3.
3
Finally, active proteinkinase 3 phosphorylates aprotein (pink) that brings about the cell’s response tothe signal.
4 Enzymes called proteinphosphatases (PP)catalyze the removal ofthe phosphate groupsfrom the proteins, making them inactiveand available for reuse.
5
The transduction stage of signaling is often a multistep process that amplifies the signal.
• About 1% of our genes are thought to code for kinases.
http://media.pearsoncmg.com/bc/bc_campbell_biology_7/media/interactivemedia/activities/load.html?11&C
Small Molecules and Ions as Second Messengers
Secondary messengers
• Are small, nonprotein, water-soluble molecules or ions
Cyclic AMP
• Many G-proteins trigger the formation of cAMP, which then acts as a second messenger in cellular pathways.
ATP
GTP
cAMP
Proteinkinase A
Cellular responses
G-protein-linkedreceptor
AdenylylcyclaseG protein
First messenger(signal moleculesuch as epinephrine)
Cyclic AMP
Cyclic AMP (cAMP)
• Is made from ATP
O–O O
O
N
O
O
O
O
P P P
PP P
O
O
O
O
O
OH
CH2
NH2 NH2 NH2
N
N
N
N
N
N
N
N
N
N
NO
O
O
ATP
Ch2 CH2
O
OH OH
P
O O
H2O
HOAdenylyl cyclase Phoshodiesterase
Pyrophosphate
Cyclic AMP AMPOH OH
O
i
3. Response
• Many possible outcomes
• This example shows a transcription response
Growth factor
Receptor
Phosphorylationcascade
Reception
Transduction
Activetranscriptionfactor Response
P
Inactivetranscriptionfactor
CYTOPLASM
DNA
NUCLEUSmRNA
Gene
• Specificity of the signal
– The same signal molecule can trigger different responses
– Many responses can come from one signal!
Signalingmolecule
Receptor
Relaymolecules
Response 1
Cell A. Pathway leadsto a single response.
Cell B. Pathway branches,leading to two responses.
Response 2 Response 3
• The signal can also trigger an activator or inhibitor
• The signal can also trigger multiple receptors and different responses
Response 4 Response 5
Activationor inhibition
Cell C. Cross-talk occursbetween two pathways.
Cell D. Different receptorleads to a different response.
Response- cell signaling leads to regulation of transcription (turn genes on or off) or cytoplasmic activities.
Long-distance Signaling - Intracellular signaling includes hormones that are hydrophobic and can cross the cell membrane.
Once inside the cell, the hormone attaches to a protein that takes it into the nucleus where transcription can be stimulated.
Testosterone acts as a transcription factor.
Hormone(testosterone)
EXTRACELLULARFLUID
Receptorprotein
DNA
mRNA
NUCLEUS
CYTOPLASM
Plasmamembrane
Hormone-receptorcomplex
New protein
• Steroid hormones– Bind to intracellular receptors
1 The steroid hormone testosterone passes through the plasma membrane.
The bound proteinstimulates thetranscription ofthe gene into mRNA.
4
The mRNA istranslated into aspecific protein.
5
Testosterone bindsto a receptor proteinin the cytoplasm,activating it.
2
The hormone-receptor complexenters the nucleusand binds to specific genes.
3
Signaling Efficiency: Scaffolding Proteins and Signaling
Complexes• Scaffolding proteins
– Can increase the signal transduction efficiency
Signalmolecule
Receptor
Scaffoldingprotein
Threedifferentproteinkinases
Plasmamembrane
Termination of the Signal
• Signal response is terminated quickly– By the reversal of ligand binding