Comparative expression of the human beta(2) and beta(3) adrenergic receptors in Saccharomyces cerevisiae

The beta(3) adrenergic receptor (beta(3)AR) is the predominant beta subtype in human brown adipocytes and is essential for regulating thermogenic lipolysis. To establish a novel experimental system for the biochemical analysis of this protein, we engineered several yeast strains. We show that the sterol background of the host strain greatly modulates the beta(3)AR expression but not in the same way as it modulates the beta(2) adrenergic receptor (beta(2)AR), the other main studied adipocyte subtype. The human beta(3)AR expressed in yeast is N-glycosylated but not phosphorylated. This latter characteristic distinguishes it from the beta(2)AR. We showed that both beta(2)AR and beta(3)AR follow the secretory pathway to the yeast plasma membrane (PM) and are degraded in the vacuole. In the yeast strains used in this work, the two receptors also share a common mechanism of direct signal transduction through the yeast G(alpha) protein, Gpa1p. These strains thus appear to be useful for biochemical and structural studies of the human beta(3)AR in an in vivo reconstitution system.