trans-Golgi retention of a plasma membrane protein: mutations in the cytoplasmic domain of the asialoglycoprotein receptor subunit H1 result in trans-Golgi retention

It has to be pointed out that even the wild-type ASGP receptor is significantly concentrated in the Golgi apparatus. By quantitative immunoelectron microscopy, ~20% of the ASGP receptor has been detected in the trans-Golgi in rat hepatocytes and in HepG2 cells (Geuze et al., 1983 (Geuze et al., , 1984 Zijderhand-Bleekemolen et al., 1987; Stoorvogel et al., 1989) . Cycloheximide, which blocks protein synthesis without affecting intracellular transport, caused depletion of poly-immunoglobulin receptor and 5'-nucleotidase from the Golgi, but did not affect the Golgi pools of the ASGP and M6P receptors (Geuze et al., 1984; van den Bosch et al., 1986) . Also by immunofluorescence microscopy, the ASGP receptor subunits in HepG2 and transfected MDCK cells can be detected in juxtanuclear Golgi-like structures, although without the obvious tubular appearance of the staining observed for Hl(A4-33A) (e.g., Fig. 2 B) . This Golgi pool of wild-type ASGP receptor may reflect an intrinsic affinity of the protein to Golgi components that is moderated by the cytoplasmic tail, and that leads to efficient Golgi retention when the cytoplasmic domain is sufficiently truncated.