Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
PowerPoint Lectures for Biology, Seventh Edition
Neil Campbell and Jane Reece
Lectures by Chris Romero
Chapter 11
Cell Communication
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Overview: The Cellular Conversation
• Cell-to-cell communication is essential for multicellular organisms
• Biologists have discovered some universal mechanisms of cellular regulation
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
External signals are converted into responses within the cell
• A signal-transduction pathway is a series of steps by which a signal on a cell’s surface is converted into a specific cellular response
• Signal transduction pathways convert signals on a cell’s surface into internal cellular responses
• Pathway similarities suggest that ancestral signaling molecules evolved in prokaryotes and have since been adopted by eukaryotes
LE 11-2 Exchange of mating factors
Mating
Receptor
a α
α factor
a α
a factor Yeast cell, mating type a
Yeast cell, mating type α
a/α
New a/α cell
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Local and Long-Distance Signaling
• Cells in a multicellular organisms communicate by chemical messengers
• Animal and plant cells have cell junctions that directly connect the cytoplasm of adjacent cells
• In local signaling, animal cells may communicate by direct contact
LE 11-3 Plasma membranes
Gap junctions between animal cells
Cell junctions
Cell-cell recognition
Plasmodesmata between plant cells
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• In many other cases, animal cells communicate using local regulators, messenger molecules that travel only short distances
• In long-distance signaling, plants and animals use chemicals called hormones
LE 11-4
Paracrine signaling
Local regulator diffuses through extracellular fluid
Secretory vesicle
Secreting cell
Target cell
Local signaling
Electrical signal along nerve cell triggers release of neurotransmitter
Neurotransmitter diffuses across synapse
Endocrine cell Blood vessel
Long-distance signaling
Hormone travels in bloodstream to target cells
Synaptic signaling
Target cell is stimulated
Hormonal signaling
Target cell
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
The Three Stages of Cell Signaling: A Preview
• Earl W. Sutherland discovered how the hormone epinephrine acts on cells
• Sutherland suggested that cells receiving signals went through three processes:
– Reception
– Transduction
– Response
LE 11-5_3
EXTRACELLULAR FLUID
Reception
Plasma membrane
Transduction
CYTOPLASM
Receptor
Signal molecule
Relay molecules in a signal transduction pathway
Response
Activation of cellular response
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
1. Reception: A signal molecule binds to a receptor protein, causing it to change shape
• The binding between a signal molecule (ligand) and receptor is highly specific
• A conformational change in a receptor is often the initial transduction of the signal
• Most signal receptors are plasma membrane proteins
LE 11-6 EXTRACELLULAR FLUID
Plasma membrane
The steroid hormone testosterone passes through the plasma membrane.
Testosterone binds to a receptor protein in the cytoplasm, activating it.
The hormone- receptor complex enters the nucleus and binds to specific genes.
The bound protein stimulates the transcription of the gene into mRNA.
The mRNA is translated into a specific protein.
CYTOPLASM
NUCLEUS
DNA
Hormone (testosterone)
Receptor protein
Hormone- receptor complex
mRNA
New protein
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• An ion channel receptor acts as a gate when the receptor changes shape
• When a signal molecule binds as a ligand to the receptor, the gate allows specific ions, such as Na+ or Ca2+, through a channel in the receptor
Ligand Gated Ion Channels
LE 11-7c
Signal molecule (ligand)
Gate closed Ions
Ligand-gated ion channel receptor
Plasma membrane
Gate closed
Gate open
Cellular response
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
2. Transduction: A series of molecular interactions relay signals from receptors to target molecules in the cell
• Transduction usually involves multiple steps
• Multistep reaction pathways can amplify a signal: A few molecules can produce a large cellular response
• Multistep pathways provide more opportunities for coordination and regulation
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Signal Transduction Pathways
• The molecules that relay a signal from receptor to response are mostly proteins
• Like falling dominoes, the receptor activates another protein, which activates another, and so on, until the protein producing the response is activated
• At each step, the signal is transduced into a different form, usually a conformational change
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Protein Phosphorylation and Dephosphorylation
• In many pathways, the signal is transmitted by a cascade of protein phosphorylations
• Phosphatase enzymes remove the phosphates, kinases add them.
• This phosphorylation and dephosphorylation system acts as a molecular switch, turning activities on and off
LE 11-8 Signal molecule
Activated relay molecule
Receptor
Inactive protein kinase
1 Active protein kinase
1
Inactive protein kinase
2 Active protein kinase
2
Inactive protein kinase
3 Active protein kinase
3
ADP
Inactive protein
Active protein
Cellular response
ATP
PP P i
ADP ATP
PP P i
ADP ATP
PP P i
P
P
P
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Cyclic AMP
• Cyclic AMP (cAMP) is one of the most widely used second messengers
• Adenylyl cyclase, an enzyme in the plasma membrane, converts ATP to cAMP in response to an extracellular signal
LE 11-13
Binding of epinephrine to G-protein-linked receptor (1 molecule)
Reception
Transduction
Inactive G protein
Active G protein (102 molecules)
Inactive adenylyl cyclase Active adenylyl cyclase (102)
ATP Cyclic AMP (104)
Inactive protein kinase A
Inactive phosphorylase kinase
Active protein kinase A (104)
Active phosphorylase kinase (105)
Active glycogen phosphorylase (106) Inactive glycogen phosphorylase
Glycogen Response
Glucose-1-phosphate (108 molecules)
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
3. Response: Cell signaling leads to regulation of cytoplasmic activities or transcription
• The cell’s response to an extracellular signal is sometimes called the “output response”
• 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 pathways regulate the activity of enzymes, turn genes on or off.
LE 11-14
Reception Growth factor
Receptor
Phosphorylation cascade
Transduction
CYTOPLASM
Inactive transcription factor
Active transcription factor
P Response
Gene
mRNA
DNA
NUCLEUS
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
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
• Insulin Signaling animation http://vcell.ndsu.nodak.edu/animations/insulinsignaling/movie-flash.htm
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Termination of the Signal
• Inactivation mechanisms are an essential aspect of cell signaling
• When signal molecules leave the receptor, the receptor reverts to its inactive state
• Cell Communication Animationshttp://www.dnalc.org/resources/3d/cellsignals.html
• http://www.youtube.com/watch?v=U6uHotlXvPo
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Pathway Mapping of EGF Signaling in a Cancer Model EGF
EGFR
EGFR
HER3
HER2
INTE
GRIN
CADH
ERIN
Caveolin
Catenin-δ
EPS15
CBL
GAB1
SRC
RhoGEF5
SHC
P85
CRKL
STAT3
ERK2
P110
RAS
RAF
SOS GRB2
MEK
Catenin-α1
PDK AKT
PLC-γ
α-Actinin
RhoGAP
Vinculin
F-Actin
PKC-δ
FAK
PXN
Cortactin
TFR
PXN
FAK
HGS
MET
MET
GSK3-α, β
EPH
Recs
ERK1 Y19
Y289
Y689
Y1422(β4)
Y132
Y251
Y657
Y88
Y198
Y207
Y204 Y187
Y1680
Y20
Y418
Y605
Y1197 Y1234
Y397
Y397 Y421
Y576
Y279, 216
Y446
Y464
Y822
Y118
Y22
Y329/334
Y1248
Y705
Y1253
Y1110
Y576
Y1207(β4)
Y783(β1)
Y998
Y318
Y1069
Y88
Y1016
Y869
Y349/350
Y280
Y771
Y313
Y1139
Y783
Y467
Y371
Y291
Y221
Y1092
Y704
Y228
Y6
Y248
Y280
Y213
Y217
Y14 Y849
Y772
Y614
Y655
Y455
Y602 Y596
Y779
Y334
Y118
Y296
SHB
Y201 Y333
Y355 Y423
Y1172
Y1328 Y797
Y570 Y427
Y575
Y628 Y608
Y594 Y1127
Cdc42
Ack p38 MAPK Y182
Y857
Y858 Y267
Crk
Y136
Y570
Y1510(β4)
DAPP1
Y139 Y154 Y141
Nck Y105
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
RAS
RAF-1
MEK1/2
ERK1/2
ELK-1, C-MYC
MNK
SHC
PLC
γ1 C
BL
SR
C GRB2
SOS
CRK
PI3K
PDK1
AKT GSK3
mTOR
JAK
STAT1
STAT3
GA
B-1
p38 MAPK
LAB
/LAT
IRS
1
IRS
2
CDC42
ACK1
JNK
C-JUN
GRB10 FAK
SPTAN1
SPRY2
SCF38
Proliferation
NF-κβ, ATF2, MNK
α α
β β
Insulin Receptor
SH
C
GR
B2
Crk
Fox0
Apoptosis
p90RSK
UV/Stress BCR
GR
B2
CB
L
Lipid Raft Aggregation
SY
K
PLCγ2
SOS VAV1
Protein Synthesis
EGFR/HER2
C-MYC
Integrins
SR
C
Pax
illin
FAK
Cell Adhesion Migration
GAB-1
γ β
Cytokine Receptor TCR GPCR
Endocytosis
p53
TfR
CSK
Ezr
in
Actin Cytoskeleton Migration
Amino Acid Transport
Rac
STAT3