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

Although the KDEL-R is normally present at lower levels in the TGN as compared to the IC and the Golgi stack, its Figure 11 . Sections of uninfected (A and B) or MHV-infected (C and D) L cells treated with SLO followed by GTP).S and double labeled with anti-KDEL-R (KR; 10 nm gold) and anti-B-COP (arrows, 5 nm gold). The COP buds/vesicles that label for the KDEL-R are indicated by arrowheads..C denotes putative clathrin coated buds/vesicles. In C and D, the structures where the assembling virions are found (large arrows, MHV) are continuous with buds/vesicles that label for B-COP and for the KDEL-R. The large arrowhead in C indicates the network of intermediate filaments that often become visible after SLO extraction. Bars, 100 nm. existence in the TGN may play a functional role. The TGN is the major site where the endocytic pathway converges with the exocytic pathway (Griffiths and Simons, 1986; Duncan and Kornfeld, 1988; Neefjes et al., 1988; Green and Kelly, 1990) , and recent studies have shown that the effects of some toxins, which enter the cell via the endocytotic pathway, depend on their COOH-terminal, KDEL-like sequence (Chaudhary et al., 1990; Pastan et al., 1992 and references therein; Pelham et al., 1992 and references therein) . Indeed, the cytotoxic activity of some toxins could be enhanced by having the KDEL sequence on the COOH terminus (Seetharam et al., 1991) . Furthermore, a KDEL-containing ER glycoprotein, calreticulin (CaBP3), acquires significant amounts of galactose, a trans-Golgi modification, in rat liver (Peter et al., 1992) . These observations, in conjunction with the localization of some KDEL-R to the TGN, suggest that KDEL receptor-mediated retrieval from this compartment may be involved in the transport of these toxins to the ER, where translocation to the cytosol has been proposed to occur (Pastan et al., 1992; Pelham et al., 1992) . A recent study by Sandvig et al. (1992) has now directly demonstrated that endocytosed Shiga toxin could be transported to the ER, most likely via the TGN and the Golgi stack.