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Scavenger receptor‐A mediates gp96/GRP94 and calreticulin internalization by antigen‐presenting cells
Author(s) -
Berwin Brent,
Hart Justin P.,
Rice Stuart,
Gass Cecilia,
Pizzo Salvatore V.,
Post Steven R.,
Nicchitta Christopher V.
Publication year - 2003
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/cdg572
Subject(s) - library science , computer science
gp96 (GRP94) elicits antigen‐presenting cell (APC) activation and can direct peptides into the cross‐ presentation pathways of APC. These responses arise through interactions of gp96 with Toll‐like (APC activation) and endocytic (cross‐presentation) receptors of APC. Previously, CD91, the α 2 ‐macroglobulin receptor, was identified as the heat shock/chaperone protein receptor of APC. Recent data indicates, however, that inhibition of CD91 ligand binding does not alter gp96 recognition and uptake. Furthermore, CD91 expression is not itself sufficient for gp96 binding and internalization. We now report that scavenger receptor class‐A (SR‐A), a prominent scavenger receptor of macrophages and dendritic cells, serves a primary role in gp96 and calreticulin recognition and internalization. gp96 internalization and peptide re‐presentation are inhibited by the SR‐A inhibitory ligand fucoidin, although fucoidin was without effect on α 2 ‐macroglobulin binding or uptake. Ectopic expression of SR‐A in HEK 293 cells yielded gp96 recognition and uptake activity. In addition, macrophages derived from SR‐A −/− mice were substantially impaired in gp96 binding and uptake. These data identify new roles for SR‐A in the regulation of cellular responses to heat shock proteins.