The cytoplasmic tail of CD1d contains two overlapping basolateral sorting signals

CD1d is a member of the CD1 polypeptide family that represents a new arm of host defense against invading pathogens. In our previous work (Rodionov, D . G., Nordeng, T. W., Pedersen, K., Balk, S. P., and Bakke, O. (1999) J. Im munol. 162, 1488-1495) we have shown that CD1d contained a classic tyrosine -based internalization signal (YQGV) in its short cytoplasmic tail. CD1d is expressed in polarized epithelial cells, and we found that the cytoplasmic tail of CDld also contained information for basolateral sorting. Interesti ngly, a mutation of the critical tyrosine residue of the endosomal sorting signal did not result in the loss of basolateral targeting of the mutant CD ld, To search for a basolateral sorting signal we have constructed a full s et of alanine mutants, but no single alanine substitution inactivated the s ignal. However, deletions or mutations of either the C-terminal valine/leuc ine pair or the critical tyrosine residue from the internalization signal a nd either residue from the C-terminal valine/leucine pair inactivated basol ateral sorting. Our data thus suggest that the cytoplasmic tail contains tw o overlapping basolateral signals, one tyrosine- and the other leucine-base d, each being sufficient to direct CDld to the basolateral membrane of pola rized Madin-Darby canine kidney cells.