Glycosylation regulates the expression of Lysosome Associated Membrane Protein-1 (LAMP1) on the cell surface

Lysosome Associated Membrane protein-1 (LAMP1) which lines the lysosomes, is often found to appear on the surface of several cells involved in migratory and/or invasive functions including metastatic tumor cells. However, the mechanism of its surface translocation in these cells is still poorly understood. Glycosylation, one of the major post-translational modifications of membrane proteins, regulates a variety of functions of such glycoproteins. The levels of poly-N-acetyllactosamine (polyLacNAc) substituted β1,6 branched Noligosaccharides on B16 melanoma variants has previously been shown to correlate with the metastatic potential of these cells. Lysosomal protein LAMP1 is one of the major carriers of these oligosaccharides and its expression on the cell surface also correlates with metastatic potential of B16 murine melanoma cells. To investigate whether these oligosaccharides have any role in increasing surface expression of LAMP1, low (B16F1) and high metastatic (B16F10) variants of B16 melanoma cells were treated with N-glycosylation inhibitor, swainsonine (SW). SW treatment resulted in significantly decreased expression of polyLacNAc substituted β1,6 branched N-oligosaccharides on these cells. This was also accompanied with significantly reduced expression of LAMP1 on the cell surface, although total levels of LAMP1 in these cells remained unaffected. This points towards a possibility that glycosylation modulates the surface expression of LAMP1 on tumor cells. The present study thus clearly underscores a novel role of N-glycosylation in regulating the surface translocation of a lysosomal membrane protein, LAMP1.