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dc.contributor.supervisor Bhullar, Rajinder P. (Oral Biology) en_US
dc.contributor.author Sidhu, Crystal
dc.date.accessioned 2016-09-15T21:24:47Z
dc.date.available 2016-09-15T21:24:47Z
dc.date.issued 2016
dc.identifier.uri http://hdl.handle.net/1993/31786
dc.description.abstract Rac1 is a member of the Rho family of low molecular mass GTP binding proteins (GTPases). It regulates the dynamics of actin cytoskeleton by causing membrane ruffling, chemotaxis, and lamellipodia formation. As is the case with other GTPases, Rac1 cycles between the active GTP-bound form and the inactive GDP-bound form. T2R4 is a bitter taste receptor that belongs to the GPCR (G-protein coupled receptor) family of proteins. In addition to mediating bitter taste sensations from the tongue, T2R4s have been recently found in tissues other than the oral cavity e.g. nasal epithelium, airways, brain, gastrointestinal tract and male reproductive system suggesting a much broader physiological function for these receptors. Quinine, an antimalarial drug is one of the most bitter tasting compounds known. Quinine is a known agonist for T2R4s whereas BCML (Nα,Nα-Bis(carboxymethyl)-L-lysine) acts as an inverse agonist. Since Rac1 is activated via various receptors like tyrosine kinase (RTKs), integrins and GPCRs; we have investigated the potential role of T2R4 in regulating Rac1 activity. In this study, HEK293T cells stably expressing T2R4/Gα16/44, T2R4 or Gα16/44 were transiently transfected with HA-Rac1 followed by treatment with quinine or quinine plus BCML for 15 min. After incubation, active Rac1 was pulled-down from cell lysate using GST-PAK1 and anti-HA monoclonal antibody was used in Western blots to quantify amount of active Rac1. The results demonstrated that quinine treatment resulted in significant (p<0.001) reduction in the amount of active Rac1 whereas in the presence of BCML, quinine failed to cause any significant change in the amount of active Rac1 when compared to untreated cells. There was no change in the level of active Rac1 when HEK293T cells stably expressing T2R4 were treated with quinine. This study is the first to show an inhibitory downstream action of a T2R4 agonist on Rac1 function. Further investigation will help in better understanding the downstream signal transduction network of T2R4 and its extra-oral physiological roles. en_US
dc.subject G protein-coupled receptor, Rac1 inactivation, Bitter taste receptor, G-alpha protein, Quinine en_US
dc.title Quinine regulates Rac1 GTPase activity through the bitter taste receptor T2R4 and G-Protein en_US
dc.degree.discipline Oral Biology en_US
dc.contributor.examiningcommittee Chelikani, Prashen (Oral Biology) Arthur, Gilbert (Biochemistry and Medical Genetics) en_US
dc.degree.level Master of Science (M.Sc.) en_US
dc.description.note October 2016 en_US


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