RIC-8B, a putative GEF of the olfactory system, interacts with Gαolf, Gβ1 e Gγ13 / Ric-8B, uma GEF putativa do sistema olfatório, interage com Gαolf, Gβ1 e Gγ13

AUTOR(ES)

Daniel Shikanai Kerr

DATA DE PUBLICAÇÃO

2008

RESUMO

The mammalian olfactory system detects small amounts of thousands of different chemical compounds. Odorant perception starts when an odorant in the air binds to an olfactory receptor (OR). ORs belong to the super family of G-protein coupled receptors (GPCRs). Even though the odorant signaling pathway is well known, little is known about its modulators. In 2005, our lab identified RIC-8B as a putative guanine nucleotide exchange factor (GEF) that is able to interact with the olfactory G-protein (Golf) and amplify its activity. Here we show that RIC-8B also interacts with Gγ13. We also found that Gβ1 is the Gβ subunit that is predominantly expressed in the olfactory epithelium. Furthermore, RIC-8B, Gαolf, Gβ1 and Gγ13 are highly concentrated in the cilia of olfactory neurons and co-localize in this cellular compartment. We also show that RIC-8B interaction with Gαolf is stronger in the presence of GDP than GTP, as expected for a GEF. Curiously, in the presence of Gβ1 and Gγ13, RIC-8B and Gαolf remain associated, in the presence of both GDP or GTP, probably through an indirect interaction via Gβ1/Gγ13. We also showed that the amounts of Gαolf, Gβ1 and Gγ13 in the cell membrane increase if RIC-8B is cotransfected in the same cell. Our results suggest that RIC-8B plays two roles. First, it may act as a chaperone which assists in the assembly and trafficking of the G protein complex. Second, RIC-8B would also act as a GEF to increase Gαolf dependent cAMP production and thereby amplify odorant signal transduction. Lastly, we believe that Gβ1 and Gγ13 may act as a scaffold to position RIC-8B close to its target, Gαolf, further enhancing the GEF activity.

ASSUNTO(S)

gpcr gpcr receptors receptores ric-8b olfactory system transdução de sinal celelar proteins g bioquímica gef gef proteínas g ric-8b biochemistry sistema olfatório olfato

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