Journal article
HSP60 is transported through the secretory pathway of 3-MCA-induced fibrosarcoma tumour cells and undergoes N-glycosylation
The FEBS journal, Vol.279(12), pp.2083-2095
2012
Abstract
There is increasing evidence localizes the mitochondrial chaperone heat shock protein (HSP)60, outside the cell, where it mediates interactions between immune cells and other body tissues. However, the mechanisms by which HSP60 is secreted into the extracellular environment are not fully understood. Recent studies have shown that HSP60 is actively released by a nonconventional secretion mechanism, the lipid raft-exosome pathway. In the present study, we show for the first time that HSP60, produced by 3-methylcholantrene-induced fibrosarcoma tumour cells, is secreted through the conventional endoplasmic reticulum-Golgi secretory pathway. Confocal microscopy using anti-TGN38 and anti-HSP60 antibodies together with monensin, a Golgi transport inhibitor, demonstrated the relocation of HSP60 to the Golgi of malignant cells but not primary fibroblast cells subjected to heat shock or fibroblast cell lines. Transmission electron microscopy, flow cytometry and cell fractionation of cell treated with brefeldin A, an inhibitor of endoplasmic reticulum to Golgi protein transport, further indicated that HSP60 is present both in the endoplasmic reticulum and the Golgi complex of malignant cells. We found a single mRNA with a mitochondrial targeting sequence encoding for HSP60 in the malignant cells but two HSP60 translation products, namely the native unmodified protein and a protein post-translationally modified by N-glycosylation. The N-glycans observed were composed of high-mannose structures and bi-, tri- and tetra-antennary complex type structures occupying sites of the three potential glycosylation sites present on HSP60. Accordingly, we propose that HSP60 in malignant cells is transported through the endoplasmic reticulum-Golgi secretion pathway, where it acquires N-glycans, and thus can affect the immunological properties of the proteins in the tumour microenvironment.
Details
- Title
- HSP60 is transported through the secretory pathway of 3-MCA-induced fibrosarcoma tumour cells and undergoes N-glycosylation
- Authors
- D Hayoun (Author) - Ben-Gurion University of the Negev, IsraelT Kapp (Author) - Ben-Gurion University of the Negev, IsraelM Edri-Brami (Author) - Ben-Gurion University of the Negev, IsraelTomer Ventura (Author) - Ben-Gurion University of the Negev, IsraelM Cohen (Author) - Ben-Gurion University of the Negev, IsraelA Avidan (Author) - Ben-Gurion University of the Negev, IsraelR G Lichtenstein (Author) - Ben-Gurion University of the Negev, Israel
- Publication details
- The FEBS journal, Vol.279(12), pp.2083-2095
- Publisher
- Wiley-Blackwell Publishing Ltd.
- Date published
- 2012
- DOI
- 10.1111/j.1742-4658.2012.08594.x
- ISSN
- 1742-464X
- Organisation Unit
- School of Science and Engineering - Legacy; University of the Sunshine Coast, Queensland; School of Science, Technology and Engineering; Centre for Bioinnovation
- Language
- English
- Record Identifier
- 99450303702621
- Output Type
- Journal article
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