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

Most mutations in secretory or membrane proteins either do not prevent surface transport or, if they perturb folding or oligomerization, cause retention and degradation in the ER. Very few mutants have been described that escape ER retention and accumulate in a Golgi compartment on the way to the cell surface. It is conspicuous that in most of these cases the mutation involves the membrane anchor of the protein or the immediate flanking sequences, which have been identified as the segments important for retention of natural Golgi resident proteins. Well characterized cases are growth hormone fused to the transmembrane and cytoplasmic domain of vesicular stomatitis virus G protein (Guan and Rose, 1984) , or to an uncleaved transmembrane segment of a GPI-anchored membrane protein (Moran and Caras, 1992) ; the insertion of an arginine into the signal/anchor domain of influenza virus neuraminidase (Sivasubramanian and Nayak, 1987) ; two point mutations close to the transmembrane segment of fowl plague virus (APN, aminopeptidase N) . The predominant intracellular localization of the constructs is indicated as in Fig. 1 (PM, plasma membrane; G, trans-Golgi structures).