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 and is retained in the ER by its COOH-terminus RDEL peptide sequence (Satoh, 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 of pHi, the cytoplasmic epitope of erd2P is not recognized by erd2P antibodies unless the cells are pretreated with NEM. Coincident with the masking of the cytoplasmic epitope of erd2P, following lowering of pHi, Hsp47 is not retained but eludes its retention receptor to be expressed on the cell surface. Alkalization of the endosomal compartments by treatment with NH4Cl or chloroquine also results in the loss of Hsp47 to the cell surface, presumably by inhibiting the retrieval of trans-Golgi network proteins from the cell surface. The expression of Hsp47 on the cell surface under conditions of stress and alteration of pHi and pHe posture Hsp47 as a serpin family protein that may modulate cell migration during development and invasion and metastasis in cancer.
Sauk
J J
JJ
Department of Pathology, Dental School and UMAB Greenbaum Cancer Center, University of Maryland at Baltimore, 21201, USA.
Norris
K
K
Hebert
C
C
Ordóñez
J
J
Reynolds
M
M
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D003593:Cytoplasm / Q000502:physiology*; D011992:Endosomes / Q000502:physiology*; D005347:Fibroblasts; D005434:Flow Cytometry; D050958:HSP47 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000096:biosynthesis / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007150:Immunohistochemistry; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D011485:Protein Binding / Q000187:drug effects; D018000:Receptors, Peptide / Q000378:metabolism*; D013347:Subcellular Fractions / Q000378:metabolism
D050958:HSP47 Heat-Shock Proteins; D006360:Heat-Shock Proteins; C064459:KDEL receptor; D008565:Membrane Proteins; D018000:Receptors, Peptide; C494661:Serpinh1 protein, mouse