DIFFERENTIAL GLYCOSYLATION AND INTRACELLULAR TRAFFICKING FOR THE LONGAND SHORT ISOFORMS OF THE D-2 DOPAMINE-RECEPTOR

The D-2 dopamine receptor exists in two alternatively spliced isoforms , ''long'' and ''short'' (D-2L and D-2S), which differ by 29 amino aci ds in the third cytoplasmic domain, The functional differences between these two isoforms are still obscure, We have performed pulse-chase s tudies on the D-2L and D-2S receptors expressed in CHO cells in order to follow the post-translational processing of the two isoforms, Both isoforms are present in three post-translational states: a newly synth esized protein, a partially glycosylated product, and a fully glycosyl ated mature 70-kDa receptor, However, the processing to the mature rec eptor differs between the two isoforms, First, the D-2S receptor is pr ocessed to the mature 70-kDa species faster than the D-2S receptor, Se cond, at 20 degrees C the D-2L isoform is fully processed to the 70-kD a species, whereas the D-2L isoform persists in its partially processe d 45-kDa state, Finally, a significant portion of the D-2L receptor re mains in its partially processed form in an intracellular compartment and does not reach the plasma membrane, These results give rise to the suggestion that the difference observed between the two alternatively spliced isoforms of the D-2 receptor may lie in their post-translatio nal processing and intracellular trafficking.