Figure 7.

Model of the differential mode of association of PAR1 with Gαi1, Gα12, and β-arrestin 1. The model is based on BRET observations and suggests the existence of two populations of PAR1, at least in COS-7 cells (Ayoub et al., 2010). In the absence of receptor activation, one population of PAR1 is preassembled with Gαi1 and another one would be non-associated with any of Gαi1, Gα12, or β-arrestin 1. A short term activation of PAR1 induces a rapid activation of the preassembled PAR1-Gαi1 complex characterized by a transient change in the relative position of PAR1 and Gαi1 without any change on free PAR1. In contrast, long term activation first results in the deactivation of the preassembled PAR1-Gαi1 complex and in parallel to the concomitant recruitment of both Gα12 and β-arrestin 1 to the activated PAR1. Interestingly, even though their similar kinetic of recruitment, Gα12 and β-arrestin 1 are not co-recruited to the same population of PAR1. Indeed, it has been clearly demonstrated that β-arrestin 1, but not Gα12, can be recruited by the activated PAR1-Gαi1 complex. In addition, it is not excluded that β-arrestin 1 is also recruited by the activated free PAR1. In contrast, after long term activation of PAR1-Gα12 seems to be translocated to the no assembled population of PAR1 only. (Adapted from Ayoub et al. (2010) Differential association modes of the thrombin receptor PAR1 with Gαi1, Gα12, and β-arrestin 1. The FASEB Journal (2010), 24(9): 3522-3535).