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1. Introduction
2. Overview of the talk
3. Engulfment of apoptotic cells
4. Signals for corpse clearance/consequences
5. Suppression of inflammation - example with J744 line
6. Long term goals
7. Markers of apoptotic cell
8. 2 functional genetic pathways regulate engulfment
9. GULP and ELMO proteins
10. Signaling via Ced-6/GULP
11. Yeast two hybrid screens with GULP
12. LRP-1 encoding clone grows in selective conditions
13. GULP binds to LRP minireceptors
14. Colocalization of overexpressed LRP and GULP
15. GST-RAP precipitates a complex of CRP and GULP
16. Disruption of LRP binding inhibits engulfment
17. Experiment with CHO cells lacking LRP1
18. Current working model for LRP mediated uptake
19. LRP+GULP actions
20. Engulfment proteins - C.elegans and mammal
21. Reciprocal activation of Rho and Rac
22. ELMO (CED-12)
23. ELMO1 - C.elegans and mammals
24. Expression of ELMO1 in different cell types
25. Defect in clearance in CED-12 mutants
26. DTC in ced deficient worms
27. Rescue of CED-12 deficiency by murine ELMO
28. Signaling model via Crk2/Dock180/ELMO complex
29. ELMO and Dock180 cooperate
30. ELMO1:Dock complex contains a GEF activity
31. Results of transfection
32. Working model
33. Rho family GEFs have tandem DH-PH domains
34. Structure of Dock180 and ELMO
35. Dock180/ELMO complex targets to membrane
36. CED-5/Dock180 binding region - role in function
37. ELMO C-term fails to localize to the membrane
38. Formation of actin rich phagocytic cup
39. Hypothesis
40. ARM repeats in ELMO/CED-12
41. Intact ARM repeats are required for uptake
42. How does ARM2 mutation localize to membrane
43. ARM2 mutation affects engulfment and migration
44. Why ARM repeats are important for engulfment
45. RhoG protein
46. RhoG signaling cascades
47. RhoG roles
48. Active RhoG translocates ELMO to the membrane
49. ARM repeats involvement in RhoG binding
50. ARM1 and -2 repeats mediate RhoG-GTP binding
51. CED-12 specifically binds active GTP band MIG-2
52. Engulfment defects are augmented in mutants
53. ELMO as a link between RhoG and Dock180
54. Summary of results
55. Overview of the mechanisms
56. Thanks

Topics Covered

• Background on engulfment of apoptotic cells
• Early lessons from the worm and graduating to mammals
• GULP and LRP1 in engulfment
• Role of ELMO and Dock180 proteins in engulfment
• The mechanisms leading to Rac activation and regulation of the cytoskeleton during engulfment

Links

Series:

• Apoptosis

Categories:

• Biochemistry
• Cell Biology

Therapeutic Areas:

• Immunology & Inflammation

Talk Citation

Ravichandran, K. (2007, October 1). Signaling during engulfment: the beginnings of a good meal [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved December 26, 2024, from https://doi.org/10.69645/EZZF1917.
Export Citation (RIS)

Publication History

• Published on October 1, 2007
• Archived on February 25, 2021

Financial Disclosures

• Prof. Kodi Ravichandran has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.