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Main Question: G protein coupled receptors are involved in highly efficient and specific activation of signalling pathways. How do GPCR signalling complexes get assembled to generate such specificity? In order to answer this question, we need to understand how receptors and their signalling partners are synthesized, folded and quality-controlled in order to generate functional proteins. Then, we need to understand how each partner of the signalling complex is selected to join a complex, and what makes this assembly possible. GPCRs are known to be able to function as oligomers, what drives the assembly into oligomers and what will be the effects of such organization on specificity and efficacy of signal transduction. Once the receptor complexes are assembled, they need to reach different locations in the cell; what drives and controls the trafficking of GPCR signalling complexes. Finally, defects in synthesis, maturation or trafficking can alter functionality of GPCRs signalling complexes; how can we manipulate the system to make it function normally again? Pharmacological chaperones may just be part of the answer to this question.
List of contents
1. ER-bound steps in the biosynthesis of G protein-coupled receptors. - 2. Role of chaperones in G protein coupled receptor signalling complex assembly. - 3. GPCR oligomerization: contribution to receptor biogenesis. - 4. The functional size of GPCRs- monomers, dimers or tetramers?. - 5. Regulation of post-Golgi traffic of G protein-coupled receptors. - 6. Regulated GPCR trafficking to the plasma membrane: general issues and the CCR5 chemokine receptor example. - 7. Regulatory Processes Governing the Cell Surface Expression of LH and FSH Receptors. - 8. Chaperone-mediated assembly of G protein complexes. - 9. Synthesis and assembly of G protein bg dimers: comparison of in vitro and in vivo studies. - 10. Preferential assembly of G-abg complexes directed by the g subunits. - 11. G Protein Trafficking. - 12. Differential assembly of GPCR signaling complexes determines signaling specificity. - 13. GPCR and voltage-gated calcium channels (VGCC) signaling complexes. - 14. Pharmacological chaperones correct misfolded GPCRs and rescue function: trafficking as a therapeutic target.
Summary
Main Question: G protein coupled receptors are involved in highly efficient and specific activation of signalling pathways. How do GPCR signalling complexes get assembled to generate such specificity? In order to answer this question, we need to understand how receptors and their signalling partners are synthesized, folded and quality-controlled in order to generate functional proteins. Then, we need to understand how each partner of the signalling complex is selected to join a complex, and what makes this assembly possible. GPCRs are known to be able to function as oligomers, what drives the assembly into oligomers and what will be the effects of such organization on specificity and efficacy of signal transduction. Once the receptor complexes are assembled, they need to reach different locations in the cell; what drives and controls the trafficking of GPCR signalling complexes. Finally, defects in synthesis, maturation or trafficking can alter functionality of GPCRs signalling complexes; how can we manipulate the system to make it function normally again? Pharmacological chaperones may just be part of the answer to this question.
