1 / 24

Chapter 6- Cell-cell communication

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.

elina
Download Presentation

Chapter 6- Cell-cell communication

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  1. 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

  2. _____________ 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 ______________)

  3. 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

  4. 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”

  5. 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

  6. 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

  7. 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

  8. 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 ____________

  9. 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

  10. C. JAK-STAT pathway- also a simpler pathway Fig. 6.21

  11. D. Wnt signaling If mutate B-catenin, constitutive activation of myc gene– Tumor formation

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

  13. 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

  14. Apoptosis is required for normal development Elegans Mammals Fig. 6.28 Apaf-1 knock-out Wild-type Fig. 6.27

  15. 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

  16. Monitoring Apoptosis by ______________ Hoechst

  17. 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

  18. Monitoring Apoptosis by _________ 1000X M38 400X Fg14 1000X Hoechst TUNEL

  19. An example of __________ signaling _________ signaling Cell 1 Delta (Ligand) Notch (receptor) Cell 2

  20. 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

  21. Integrins interact with both extracellular and intracellular scaffolds Fibronectin Integrin Actin

  22. 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 _______________

  23. 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

  24. LPB 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?

More Related