Localization of the Lys, Asp, Glu, Leu tetrapeptide receptor to the Golgi complex and the intermediate compartment in mammalian cells

The finding that a significant amount of the KDEL receptor is present in both the IC and the Golgi stack means that the receptor is concentrated in at least two distinct functional compartments that are connected by vesicular transport, at least in the anterograde direction. This observation is significant since it is consistent with the generally accepted model for KDEL receptor function. Accordingly, the receptor would bind ligand in a downstream compartment and recycle it back to an upstream organelle that, by definition, must have a different lumenal environment necessary for the ligand to dissociate (Munro and Pelham, 1987; Pelham, 1988 Pelham, , 1989 . A recent study has shown that the binding of KDEL ligands to Golgi membranes in vitro is enhanced at relatively low pH (,05) . Although this suggests that pH may be an important factor for binding in vivo, this notion is hard to reconcile with other lines of evidence that argue in favor of a neutral pH in the pre-TGN compartment(s) of the Golgi complex (Griffiths and Simons, 1986; Anderson and Orci, 1988) . In this study, bafilomycin A1 had no effect on the distribution of the receptor. While the precise role of pH in the binding of KDEL ligands to the receptor in the cell remains to be elucidated, our data argue that the "downstream" organelle where the KDEL-R binds its ligands is the Golgi complex, while the upstream (dissociation) organelle would be the IC. The number of compartments comprising the Golgi is still controversial (see Mellman and Simons, 1992) . However, the finding of low but variable labeling for the KDEL-R in the TGN would necessitate, at a minimum, one additional recycling step from the TGN back to earlier compartments.