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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.

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Chapter 6 cell cell communication l.jpg
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


Slide2 l.jpg

_____________ interaction-Tissue A requires tissue B to respond in a certain way (analogy to a book _______________)

  • Instructive vs permissive interactions

____________ 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 ______________)


Slide3 l.jpg

Epithelial-mesenchymal interactions

Fig. 6.7

  • __________- sheets of cells from any germ layer

  • ____________- unconnected cells (from mesoderm or neural crest)

  • All organs have both of these cell types

Mesen-

chyme

Wing

epithelium

Wing

_______

specificity

Thigh

Epithelial-mesenchymal interactions

Foot

________

specificity

Thus, mesenchyme __________ epithelium


Slide4 l.jpg

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”


Paracrine factors l.jpg
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


Other well known paracrine factors l.jpg
Other well-known paracrine factors

  • _________ family- (3 in vertebrates)-create boundaries, induce development

  • _____ family- (15 in vertebrates)- limb polarity, muscle development

  • _________ superfamily (>30 members)- bone, kidney, neuronal , etc. differentiation


Slide7 l.jpg

Cell surface receptor pathways

BLA512 1/5/98 update

Smad

Smad

Smad

Smad

STAT

STAT

STAT

STAT

Elk-1

NFkB

CREB

Gene

Fos

Fos

jun

jun

AP1

AP1

P

P

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)

PLCb

DAG

MEKK

(a MAPKKK)

NIK

AMP

cAMP

MAPKK

(e.g.MEK)

PKC

JNKK

IKK

PKA

Caspases

JNK

IkB/NFkB

IkB/NFkB

MAP-kinase (ERK)

Cell death

Elk-1

jun

JNK

Gene

Gene

Nucleus

Gene

Gene


Signal transduction pathways l.jpg
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 ____________


Slide9 l.jpg

B. TGF-b signalling- a simpler pathway

  • Ligand binds _______

  • Two _______ receptors dimerize

  • _____________________occurs

  • Receptor phosphorylates ________

  • SMADs ___________

  • SMADs enter _________and bind ____

  • Transcription is _____________

Fig. 6.20



Slide11 l.jpg

D. Wnt signaling

If mutate B-catenin, constitutive activation of myc gene– Tumor formation


Slide12 l.jpg

Apoptosis

Jacobson et al., Cell 88:347 (1997)


Slide13 l.jpg

Fas-null mice

Lymph

nodes

Spleen

Too much and too little

  • Too much- ________________ disease

    • Alcohol-induced liver disease

    • Autoimmune disease

    • Primary biliarry cirrhosis

    • Wilson’s disease

    • Ischemia reperfusion injury

    • Virus hepatitis

  • Too little- ___________

    • Splenomegaly

    • Lymphadenopathy

    • Cholangiocarcinoma

    • Hepatocellular Carcinoma


Slide14 l.jpg

Apoptosis is required for normal development

Elegans

Mammals

Fig. 6.28

Apaf-1 knock-out

Wild-type

Fig. 6.27


Slide15 l.jpg

  • Cleavage of Death substrates

  • structural proteins (e.g. actin)

  • kinases (e.g. MEKK, PKC)

  • cell cycle proteins (pRb, PARP)

  • DNA repair enzymes

  • DNA nucleases

  • Anti-apoptotic proteins (Bcl-2)

Receptor-mediated Apoptosis

Caspases-3, -6 and -7

Protective



Slide17 l.jpg

0h

0h

3h

3h

Monitoring Apoptosis by _______________

Fg-14

1000 bp ladder

M38

100 bp ladder

7h

7h

5 kb

2 kb

1 kb

0.5kb


Slide18 l.jpg

Monitoring Apoptosis by _________

1000X

M38

400X

Fg14

1000X

Hoechst

TUNEL


An example of signaling l.jpg
An example of __________ signaling

_________ signaling

Cell 1

Delta (Ligand)

Notch (receptor)

Cell 2


Another example of signaling l.jpg
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



Another form of communication transmission of signals through l.jpg
Another form of communication- scaffolds_______transmission of signals through __________________

Fig. 6.38

  • Does not requires a __________, only regulation of small molecules through a port

  • Ports are composed of _______________


Slide23 l.jpg

Example: Two pathways direct lymphocyte development

Point of _________

Fig. 6.40


Slide24 l.jpg

LPB scaffolds

LPS

FasL

TNF

CD14

TNFR

TLR-4

FasR

FADD

IL1R1

TRADD

FADD

Caspase 8

Caspase 8

TAK1

RIP

TGFBR

TRAF2

P38 MAPK

MyD88

Sorb.

P38 MAPK

NIK

TRAF6

IRAK

TNF

TPL-2

MEKK1, 2, 3

PKC

EGFR

JNKK

IKK

MEK

Calyculin A,

Okadaic Acid

JNK

PD098059

p65

ERK1,2

PDTC

c-jun

ALLN, HMA

p105

Apoptosis

IkB

NF-kB

Proteasome

SN50

P105 phos, degraded

NF-kB-responsive genes

ROS

A1, A20, ,Fas, FasL,TNF, Bcl2,

TRAF1,2, c-IAP1,2

LPS-mediated apoptosis: Which pathway is defective?


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