Retinoic acid alters the intracellular trafficking of the mannose-6-phosphate/insulin-like growth factor II receptor and lysosomal enzymes
| Autor: | Roshantha A.S. Chandraratna, Jing X. Kang, Jennifer Bell, Richard L. Beard, Alexander Leaf |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
Retinoic acid
Fluorescent Antibody Technique Tretinoin Mannose 6-phosphate Biology Cathepsin B Receptor IGF Type 2 chemistry.chemical_compound Keratolytic Agents medicine Animals Receptor Cells Cultured Multidisciplinary Insulin-like growth factor 2 receptor Biological Transport Fibroblasts Biological Sciences Molecular biology Rats chemistry Nuclear receptor Lysosomes Intracellular medicine.drug |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America. 95(23) |
| ISSN: | 0027-8424 |
| Popis: | Previously, we showed that retinoic acid (RA) binds to the mannose-6-phosphate/insulin-like growth factor II receptor (M6P/IGF2R) with high affinity, suggesting that M6P/IGF2R may be a receptor for RA. Here, we show that RA, after 2–3 h of incubation with cultured neonatal-rat cardiac fibroblasts, dramatically alters the intracellular distribution of M6P/IGF2R as well as that of cathepsin B (a lysosomal protease bearing M6P). Immunofluorescence techniques indicate that this change in intracellular distribution is characterized by a shift of the proteins from the perinuclear area to cytoplasmic vesicles. The effect of RA was neither blocked by an RA nuclear receptor antagonist (AGN193109) nor mimicked by a selective RA nuclear-receptor agonist (TTNPB). Furthermore, the RA-induced translocation of cathepsin B was not observed in M6P/IGF2R-deficient P388D1 cells but occurred in stably transfected P388D1 cells expressing the receptor, suggesting that the effect of RA might be the result of direct interaction with M6P/IGF2R, rather than the result of binding to the nuclear receptors. These observations not only support the idea that M6P/IGF2R mediates an RA-response pathway but also indicate a role for RA in control of intracellular trafficking of lysosomal enzymes. Therefore, our observations may have important implications for the understanding of the diverse biological effects of retinoids. |
| Databáze: | OpenAIRE |
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