Signal-Mediated Cellular Retention and Subunit Assembly of Human Acetylcholinesterase
Kinetic analysis of human AChE T- subunit secretion by 293-HEK cells revealed preferential secretion of assembled dimers (Kerem et al., 1993). Secretion of ER resident enzymes is precluded through a signal mediated process involving a membrane-bound receptor (Munro and Pelham, 1987) which recognizes a specific signal at the COOH-termi-nus of the lumenal proteins (Pelham, 1990) of which the Acid-Leu terminus appears to be the most critical structural element in the interaction between the ER lumenal proteins and their cognate receptor (Pelham, 1990; Andres et al., 1991). The presence of a CSDL motif at the C-terminus of the AChE polypeptide could suggest the participation of a selective signal-mediated ER retrieval process in the preferential export of assembled AChE catalytic subunits. To examine this possibility, secreted and cell-associated enzymatic activities in transiently transfected cells expressing HuAChE carboxyl-terminus mutants were determined (See Table 1).