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The adhesion GPCRs CELSR1-3 and LPHN3 engage G proteins via distinct activation mechanisms
The adhesion GPCRs CELSR1-3 and LPHN3 engage G proteins via distinct activation mechanisms
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Length:
20 minutes
Released:
Apr 3, 2023
Format:
Podcast episode
Description
Link to bioRxiv paper:
http://biorxiv.org/cgi/content/short/2023.04.02.535287v1?rss=1
Authors: Bui, D. L. H., Roach, A., Li, J., Bandekar, S. J., Orput, E., Raghavan, R., Arac, D., Sando, R.
Abstract:
Adhesion GPCRs (aGPCRs) are a large GPCR class that direct diverse fundamental biological processes. One prominent mechanism for aGPCR agonism involves autoproteolytic cleavage, which generates an activating, membrane-proximal tethered agonist (TA). How universal this mechanism is for all aGPCRs is unclear. Here, we investigate G protein induction principles of aGPCRs using mammalian LPHN3 and CELSR1-3, members of two aGPCR families conserved from invertebrates to vertebrates. LPHNs and CELSRs mediate fundamental aspects of brain development, yet CELSR signaling mechanisms are unknown. We found that CELSR1 and CELSR3 are cleavage-deficient, while CELSR2 is efficiently cleaved. Despite differential autoproteolysis, CELSR1-3 all engage GS, and CELSR1 or CELSR3 TA point mutants retain GS coupling activity. CELSR2 autoproteolysis enhances GS coupling, yet acute TA exposure alone is insufficient. These studies support that aGPCRs signal via multiple paradigms and provide insights into CELSR biological function.
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Podcast created by Paper Player, LLC
http://biorxiv.org/cgi/content/short/2023.04.02.535287v1?rss=1
Authors: Bui, D. L. H., Roach, A., Li, J., Bandekar, S. J., Orput, E., Raghavan, R., Arac, D., Sando, R.
Abstract:
Adhesion GPCRs (aGPCRs) are a large GPCR class that direct diverse fundamental biological processes. One prominent mechanism for aGPCR agonism involves autoproteolytic cleavage, which generates an activating, membrane-proximal tethered agonist (TA). How universal this mechanism is for all aGPCRs is unclear. Here, we investigate G protein induction principles of aGPCRs using mammalian LPHN3 and CELSR1-3, members of two aGPCR families conserved from invertebrates to vertebrates. LPHNs and CELSRs mediate fundamental aspects of brain development, yet CELSR signaling mechanisms are unknown. We found that CELSR1 and CELSR3 are cleavage-deficient, while CELSR2 is efficiently cleaved. Despite differential autoproteolysis, CELSR1-3 all engage GS, and CELSR1 or CELSR3 TA point mutants retain GS coupling activity. CELSR2 autoproteolysis enhances GS coupling, yet acute TA exposure alone is insufficient. These studies support that aGPCRs signal via multiple paradigms and provide insights into CELSR biological function.
Copy rights belong to original authors. Visit the link for more info
Podcast created by Paper Player, LLC
Released:
Apr 3, 2023
Format:
Podcast episode
Titles in the series (100)
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