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Received for publication September 24, 2004.
Revised November 26, 2003.
Accepted for publication December 3, 2003.
1D-adrenergic receptor prevents cell surface expression
We previously reported that truncation of the N-terminal 79 amino acids of 
1D-adrenoceptors (
1-791D-ARs) greatly increases binding site density. In this study, we determined if this effect was associated with changes in 1D-AR subcellular localization. Confocal imaging of GFP-tagged receptors and sucrose density gradient fractionation suggested that full-length 1D-ARs were found primarily in intracellular compartments, while 1-791D-ARs were translocated to the plasma membrane. This resulted in a 3-4 fold increase in intrinsic activity for stimulation of inositol phosphate formation by norepinephrine. We determined whether this effect was transplantable by creating N-terminal chimeras of 1-ARs containing the body of one subtype and the N-terminus of another (1ANT-D; 1BNT-D; 1DNT-A; and 1DNT-B). When expressed in HEK293 cells, radioligand binding revealed that binding densities of
1A- or 1B-ARs containing the 1D-N-terminus decreased by 86-93%, whereas substitution of
1A- or 1B-N-termini increased 1D-AR binding site density by 2-3-fold. Confocal microscopy showed that GFP-tagged 1DNT-B-ARs were found only on the cell surface while GFP-tagged 1BNT-D-ARs were completely intracellular. Radioligand binding and confocal imaging of GFP-tagged 1D- and 1-791D-ARs expressed in rat aortic smooth muscle cells produced similar results, suggesting these effects are generalizable to cell types that endogenously express 1D-ARs. These findings demonstrate that the N-terminal region of 1D-ARs contain a transplantable signal that is critical for regulating formation of functional bindings, through regulating cellular localization.
Key words:
adrenergic receptor, epinephrine, inositol phosphates, norepinephrine, smooth muscle, surface expression
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