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The cation‐independent mannose 6‐phosphate receptor is involved in lysosomal delivery of serglycin
Author(s) -
Lemansky Peter,
Fester Ines,
Smolenova Eva,
Uhländer Christoph,
Hasilik Andrej
Publication year - 2007
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0806520
Subject(s) - proteoglycan , mannose , cycloheximide , mannose 6 phosphate receptor , biochemistry , biology , glycosylation , tunicamycin , receptor , lysosome , microbiology and biotechnology , sulfation , mannose 6 phosphate , mannose receptor , cathepsin d , macrophage , protein biosynthesis , growth factor , enzyme , extracellular matrix , unfolded protein response , endoplasmic reticulum , in vitro
To clarify the sorting mechanism of the lysosomal/granular proteoglycan serglycin, we treated human promonocytic U937 cells with p‐nitrophenyl‐β‐D‐xyloside (PNP‐xyl) and cycloheximide. In the absence of protein synthesis, the carbohydrate moiety of serglycin was synthesized as PNP‐xyl‐chondroitin sulfate (CS), and most of it was delivered to lysosomes and degraded. Further, an augmented lysosomal targeting of serglycin in the presence of tunicamycin suggested that a sorting/lectin receptor with multiple specificity was involved with an increased capacity for serglycin in the absence of N‐glycosylation. Correspondingly, the cation‐independent mannose 6‐phosphate receptor (CI‐MPR) and sortilin were observed to bind to immobilized CS. These receptors were eluted in the presence of 200–400 mM and 100–250 mM NaCl, respectively. After treating the cells with a cross‐linking reagent, a portion of the sulfated proteoglycan was coimmunoprecipitated with the CI‐MPR but not with sortilin. In the presence of phorbol ester, lysosomal targeting of serglycin and to a lesser extent, of cathepsin D was inhibited. We conclude that the CI‐MPR participates in lysosomal and granular targeting of serglycin and basic proteins such as lysozyme associated with the proteoglycan in hematopoietic cells.