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Have Receptor, Need Function

LYVE-1, lymphatic vessel endothelial hyaluronan receptor-1, is a transmembrane glycoprotein that is selectively expressed in the endothelium of lymphatic capillaries. Because it contains a prototypic hyaluronan-binding domain, it is believed that the receptor may function in hyaluronan clearance and hyaluronan-mediated leukocyte adhesion. However, recent experiments have shown that mice lacking LYVE-1 have normal serum and tissue hyaluronan levels and that hyaluronan-mediated adhesion/migration events proceed as usual.

TNF induces uptake and degradation of LYVE-1.

To explain this observation, Louise A. Johnson and colleagues explored the possibility that LYVE-1 functions specifically during inflammation. They found that rather than activating the receptor, pro-inflammatory cytokines down-regulate it by inducing its internalization and degradation. Moreover, they show that internalization does not trigger LYVE-1 binding to or transport of hyaluronan, indicating that the process is not causally linked to hyaluronan metabolism. These results suggest that LYVE-1 does not function as an overt receptor for hyaluronan in either inflamed or uninflamed lymphatic endothelium and raise the possibility that this abundant protein has another as yet undefined function in lymphangiogenesis.

FOOTNOTES

See referenced article, J. Biol. Chem. 2007, 282, 33671-33680

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