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1. Introduction
2. Outline
3. Overview
4. Ryanodine receptor - an overview
5. Molecular cloning of human RyR2
6. Complexity of RyR function
7. RyR domain architecture
8. RyR channel regulation
9. Intrinsic lattice formation of RyR tetramers
10. "Coupled gating": synchronous channel opening
11. Regulators of RyR channel activity
12. Channel regulation by divalent cations
13. Regulation by phosphorylation
14. Regulation by protein-protein interaction
15. Building a picture of RyR domain localization
16. Leucine zippers (LZ) and coiled-coil domains
17. Coiled-coil domains: stitching monomers together
18. Role of LZ motifs in RyR protein-protein interaction
19. Creation of cellular 'super-networks'
20. Disruption of the RyR macromolecular complex
21. A 'unifying' mechanism of pathological Ca leak
22. Genetic basis of RyR dysfunction
23. Mutations in EC coupling: arrhythmogenic culprits
24. The genetic basis of stress-induced VT
25. Novel mutations identified over the years
26. Ryanodine receptor mutations
27. Ryanodine receptor mutations clustering
28. Amino acid changes exhibit locus specificity
29. Effect of mutations loci on functional defects
30. The molecular basis of RyR-linked diseases
31. The basis of skeletal muscle pathologies
32. Molecular basis of malignant hyperthermia
33. The use of recombinant systems
34. Experimental systems: HL-1 cells
35. HL-1 cardiomyocytes: a functional syncitium
36. Monitoring intracellular expression
37. Visualising RyR2 in cardiomyocytes
38. Mechanistic defects in RyR2 mutants
39. Molecular aspects of RyR2-linked arrhythmia
40. Domain 'unzipping' and channel instability
41. Telling proteins apart...
42. Fluorescence resonance energy transfer (FRET)
43. Interacting (I-) domain: a molecular 'hinge'
44. The link between channel opening and Ca release
45. Summary

Topics Covered

• Molecular cloning of RyR
• The identification of functional domains
• RyR channel structure
• Channel regulation by: a) inter-RyR interaction, b) divalent cations and c) protein:protein interactions
• The role of leucine zippers in assembling the 'macromolecular complex'
• Defective protein:protein interactions in cardiac disease
• Genetic basis of RyR dysfunction
• Identification of mutations in cardiac RyR
• Functional characterization of RyR mutations
• Investigating interdomain interactions using state-of-the-art imaging tools
• Pathological defects in channel stability

Links

Series:

• Calcium Signaling I

Categories:

• Biochemistry
• Cell Biology

Therapeutic Areas:

• Cardiovascular & Metabolic

Talk Citation

George, C. and Lai, F.A. (2022, May 9). Molecular biology of ryanodine receptors: an overview [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved November 21, 2024, from https://doi.org/10.69645/UMJR9240.
Export Citation (RIS)

Publication History

• Published on October 1, 2007
• Reviewed on May 9, 2022

Financial Disclosures

• Dr. Christopher George has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.
• Prof. F. Anthony Lai has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.