Chapter 6- Cell-cell communication

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Chapter 6- Cell-cell communication
More definitions
_________-interaction between two or more
distinct cells or tissues
_________- the cell of tissue producing the
signal __________- the cell or tissue being
induced
_________ the ability to respond to a given
inducer
Fig. 6.2
Example- Pax6 is required for optic vesicle to
respond to an inducer, but Pax6 is not the
inducer
Lacking nose and eyes
Hence, Pax6 makes cells _____________
Pax6 null
Wild-type
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• Instructive vs permissive interactions

_____________ interaction-Tissue A requires
tissue B to respond in a certain way (analogy to
a book _______________)
____________ interaction-Tissue A does not
require tissue B to respond in a certain way, but
only needs to be in a certain environment
(analogy to a book ______________)
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Epithelial-mesenchymal interactions

• __________- sheets of cells from any germ layer
• ____________- unconnected cells (from mesoderm or
  neural crest)
• All organs have both of these cell types

Fig. 6.7
Mesen- chyme
Wing epithelium
Wing
_______ specificity
Thigh
Epithelial-mesenchymal interactions
Foot
________ specificity
Thus, mesenchyme __________ epithelium
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Epithelial-mesenchymal interactions
Newt with tadpole suckers
Regional specificity
Epithelial-mesenchymal interactions
_______ specificity
Frog gastrula
Newt gastrula
Thus, mesenchyme dictates _______ type, but
epithelium dictates ____ of the organ
Newt gastrula
Frog gastrula
Frog with newt balancers
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Paracrine factors
__________factors- diffusible molecules that can
travel small distances to signal a neighboring
cell __________signaling- cell-cell interactions
by direct contact
Example of _________ signaling
Fibroblast growth factor (FGF) binds FGF
receptors (FGFRs) These are receptor tyrosine
kinases
FGF (________)
FGFR (______)
__________________ yields activation and
subsequent phosphorylation of a second protein
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Other well-known paracrine factors

• _________ family- (3 in vertebrates)-create
  boundaries, induce development
• _____ family- (15 in vertebrates)- limb polarity,
  muscle development
• _________ superfamily (gt30 members)- bone,
  kidney, neuronal , etc. differentiation

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Cell surface receptor pathways
BLA512 1/5/98 update
Enzyme-linked
Ion channel-linked No details shown
G-protein-linked
PDGF, EGF, IFa,b,and g, IL-2 ,IL-3, IL-4, IL-6
TNFa
TGF-b
PLCg
Grb2
Jak
G proteins
TRADD
Gs Golf
FADD
Gq Go
GNRPs (e.g. Sos)
TRAF
Complexity!
Ca from ER
Ras
IP3
PIP
Adenylyl cyclase
Cytoplasm
Raf (a MAPKKK)
DAG
PLCb
MEKK (a MAPKKK)
NIK
cAMP
AMP
MAPKK (e.g.MEK)
PKC
JNKK
IKK
PKA
Caspases
JNK
IkB/NFkB
MAP-kinase (ERK)
IkB/NFkB
Cell death
Elk-1
jun
JNK
Gene
Gene
Nucleus
Gene
Gene
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Signal transduction pathways
Phosphorylation is key
General pathway
Fig. 6.14
A. Receptor tyrosine kinase (RTK)

• ________ binds receptor
• Receptor undergoes _______
• Receptor ____________ occurs
• Receptor __________________
• Receptor binds _____________
• Adaptor protein binds ________
• G-protein recruits ____
• Raf phophorylates ____
• ____ phosphorylates ERK
• ERK phosphoryates a
• ____________________
• Transcription is ____________

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B. TGF-b signalling- a simpler pathway

1. Ligand binds _______
2. Two _______ receptors dimerize
3. _____________________occurs
4. Receptor phosphorylates ________
5. SMADs ___________
6. SMADs enter _________and bind ____
7. Transcription is _____________

Fig. 6.20
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C. JAK-STAT pathway- also a simpler pathway
Fig. 6.21
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D. Wnt signaling
If mutate B-catenin, constitutive activation of
myc gene Tumor formation
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Apoptosis
Jacobson et al., Cell 88347 (1997)
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Too much and too little

• Too much- ________________ disease
• Alcohol-induced liver disease
• Autoimmune disease
• Primary biliarry cirrhosis
• Wilsons disease
• Ischemia reperfusion injury
• Virus hepatitis

• Too little- ___________
• Splenomegaly
• Lymphadenopathy
• Cholangiocarcinoma
• Hepatocellular Carcinoma

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Apoptosis is required for normal development
Elegans
Mammals
Fig. 6.28
Apaf-1 knock-out
Wild-type
Fig. 6.27
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Receptor-mediated Apoptosis
Caspases-3, -6 and -7
Protective
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Monitoring Apoptosis by ______________
Hoechst
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Monitoring Apoptosis by _______________
1000 bp ladder
Fg-14
M38
100 bp ladder
7h
7h
5 kb
2 kb
1 kb
0.5kb
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Monitoring Apoptosis by _________
1000X
M38
400X
Fg14
1000X
Hoechst
TUNEL
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An example of __________ signaling
_________ signaling
Cell 1
Delta (Ligand)
Notch (receptor)
Cell 2
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Another example of ____________ signaling
The ___________________

• The stuff between cells
• Affects cell adhesion, _______________,
  epithelial sheet formation
• Includes collagen, proteoglycans, fibronectin and
  laminin

_______ are the _______________ for extracellular
matrix molecules
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Integrins interact with both extracellular and
intracellular scaffolds
Fibronectin
Integrin
Actin
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Another form of communication- _______transmission
of signals through __________________
Fig. 6.38

• Does not requires a __________, only regulation
  of small molecules through a port
• Ports are composed of _______________

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Signaling pathways exhibit ____________- A major
challenge in biology- How to get specificity from
_______________pathways
Example Two pathways direct lymphocyte
development
Point of _________
Fig. 6.40
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LPS-mediated apoptosis Which pathway is
defective?