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

Our understanding of the molecular role of the KDEL sequence has been enhanced significantly by the identification of the yeast ERD2 gene that encodes the HDEL receptor Semenza et al., 1990) . Furthermore, the ERD2 gene product is also essential for proper functioning of the Golgi apparatus and the secretory pathway in general (Semenza et al., 1990) . Two closely related mammalian homologues have been cloned Hsu et al., 1992; Tang et al., 1993) . The deduced amino acid sequence predicts that the KDEL receptor is an integral membrane protein having seven hydrophobic regions and a molecular mass of ,'~ 23 kD, which has been confirmed by immunoblotting analysis using a specific antibody . We have recently proposed that the KDEL receptor (KDEL-R) is an integral membrane protein containing six transmembrane domains with both NH2 and COOH termini on the cytoplasmic side of the membrane (Singh et al., 1993) , although a topology with seven transmembrane domains has also been suggested (Townsley et al., 1993) . The fact that this molecule indeed functions as the KDEL receptor has now been established by evidence from genetic Semenza et al., 1990) , biochemical Wilson et al., 1993) , and cell biological (Lewis and Pelham, 1992) approaches. An important question that remains unresolved concerns the ultrastructural localization of the receptor, a question that is the main focus of this paper.