Targeting of protein ERGIC-53 to the ER/ERGIC/cis-Golgi recycling pathway

Within the secretory pathway there is precedence for targeting mediated by lumenal, transmembrane, and cytoplasmic domains acting alone or in combination (Nilsson et al., 1989; Munro, 1991; Sweet and Pelham, 1992; Ponnambalam et al., 1994; Schweizer et al., 1994) . To test the contribution to targeting of each domain of ERGIC-53 we have chosen human CD4, a monomeric, N-glycosylated plasma membrane protein as a reporter. To test sufficiency for correct targeting of the lumenal domain of ER-GIC-53 we replaced its transmembrane with that of CD4 and substituted the cytoplasmic domain with alanines ( Fig. 1., L53T4R2Alo) . Targeting sufficiency of the transmembrane domain was tested by replacing the transmembrane domain in CD4 by that of ERGIC-53 (Fig. 1, L4T53C4) .