HSP47 BINDS TO THE KDEL RECEPTOR AND CELL-SURFACE EXPRESSION IS MODULATED BY CYTOPLASMIC AND ENDOSOMAL PH

Hsp47 is a novel glycoprotein that binds specifically to procollagen a nd is retained in the ER by its COOH-terminus RDEL peptide sequence (S atoh, M. et al. Jol. Cell. Biol. 1996; 133: 469-83). In this paper, we report that erd2P, the KDEL receptor, is distributed, coprecipitates with, and binds to Hsp47, Also, under stress conditions and lowering o f pH(i), the cytoplasmic epitope of erd2P is not recognized by erd2P a ntibodies unless the cells are pretreated with NEM. Coincident with th e masking of the cytoplasmic epitope of erd2P, following lowering of p H(i), Hsp47 is not retained but eludes its retention receptor to be ex pressed on the cell surface. Alkalization of the endosomal compartment s by treatment with NH4Cl or chloroquine also results in the loss of H sp47 to the cell surface, presumably by inhibiting the retrieval of tr ans-Golgi network proteins from the cell surface. The expression of Hs p47 on the cell surface under conditions of stress and alteration of p H(i) and pH(e) posture Hsp47 as a serpin family protein that may modul ate cell migration during development and invasion and metastasis in c ancer.