TRANSMEMBRANE DOMAIN MUTATIONS INFLUENCE THE CELLULAR-DISTRIBUTION OFLYSOSOMAL MEMBRANE GLYCOPROTEIN-A

The Igp/LAMP family of mammalian and avian lysosomal type I membrane g lycoproteins features short, conserved, cytosolic tails that possess l ysosomal targeting information. The sequences of the adjacent transmem brane domains are also highly conserved, with six amino acids identica l in all sixteen known Igp variants. These six residues are found alon g one side of a hypothetical alpha-helix that may comprise this domain . We substituted or deleted some of the conserved transmembrane residu es in mouse Igp-A and stably expressed the proteins in Chinese hamster ovary cells. We examined various properties and transport characteris tics of the normal and modified proteins and concluded that the transm embrane domain serves as more than just a membrane anchor, as it subtl y influences the cellular distribution of the protein as well. (C) 199 6 Academic Press, Inc.