Abstract
Purified Signal Recognition Protein (SRP) has previously been shown to be required for the translocation of secretory proteins across the microsomal membrane (Walter and Blobel, 1980. Proc. Natl. Acad. Sci. U. S. A. 77:7, 112-7, 116) and to function in the early events of this process (Walter and Blobel, 1981. J. Cell Biol. 91:557-561). We demonstrate here that the delta subunit of acetylcholine receptor (AChR-delta), a transmembrane glycoprotein, likewise requires SRP for its asymmetric integration into microsomal membranes. We further demonstrate by partial sequence analysis that AChR-delta is synthesized with a transient NH2-terminal signal sequence of 21 residues that is cleaved off during integration into microsomal membranes. Integration of AChR-delta into the microsomal membrane vesicles proceeded asymmetrically, yielding a large (44 kdalton) core-glycosylated domain, inaccessible to externally added proteolytic enzymes and a smaller (approximately 16 kdalton) domain exposed on the outside of the vesicles and accessible to externally added proteolytic enzymes. The NH2 terminus of the molecule is contained in the 44-kdalton domain.