Low signaling efficiency from receptor to effector in olfactory transduction: A quantified ligand-triggered GPCR pathway.
Proc Natl Acad Sci U S A
; 119(32): e2121225119, 2022 08 09.
Article
em En
| MEDLINE
| ID: mdl-35914143
ABSTRACT
G protein-coupled receptor (GPCR) signaling is ubiquitous. As an archetype of this signaling motif, rod phototransduction has provided many fundamental, quantitative details, including a dogma that one active GPCR molecule activates a substantial number of downstream G protein/enzyme effector complexes. However, rod phototransduction is light-activated, whereas GPCR pathways are predominantly ligand-activated. Here, we report a detailed study of the ligand-triggered GPCR pathway in mammalian olfactory transduction, finding that an odorant-receptor molecule when (one-time) complexed with its most effective odorants produces on average much less than one downstream effector. Further experiments gave a nominal success probability of tentatively â¼10-4 (more conservatively, â¼10-2 to â¼10-5). This picture is potentially more generally representative of GPCR signaling than is rod phototransduction, constituting a paradigm shift.
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Base de dados:
MEDLINE
Assunto principal:
Olfato
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Transdução de Sinais
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Receptores Odorantes
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Receptores Acoplados a Proteínas G
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Ligantes
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Odorantes
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article