Mouse LYVE-1 is an endocytic receptor for hyaluronan in lymphatic endothelium

The glycosaminoglycan hyaluronan is a key substrate for cell migration in tissues during inflammation, wound healing, and neoplasia. Unlike other matrix components, hyaluronan (HA) is turned over rapidly, yet most degradation occurs not locally but within distant lymph nodes, through mechanisms that...

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Bibliographic Details
Published in:The Journal of biological chemistry Vol. 276; no. 22; p. 19420
Main Authors: Prevo, R, Banerji, S, Ferguson, D J, Clasper, S, Jackson, D G
Format: Journal Article
Language:English
Published: United States 01.06.2001
Subjects:
Amino Acid Sequence
Animals
Base Sequence
Biotinylation
Blotting, Northern
Cell Line
Cell Movement
Cloning, Molecular
Databases, Factual
Dose-Response Relationship, Drug
Endothelium - metabolism
Endothelium, Vascular - metabolism
Expressed Sequence Tags
Female
Fibroblasts - metabolism
Glycoproteins - chemistry
Glycoproteins - genetics
Glycoproteins - physiology
Glycosaminoglycans - metabolism
Humans
Hyaluronan Receptors - genetics
Hyaluronan Receptors - metabolism
Hyaluronic Acid - metabolism
Hyaluronic Acid - pharmacokinetics
Lymph Nodes - metabolism
Lymphangioma - metabolism
Membrane Transport Proteins
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Knockout
Microscopy, Fluorescence
Microscopy, Immunoelectron
Molecular Sequence Data
Neoplasm Transplantation
Plasmids - metabolism
Protein Binding
Recombinant Fusion Proteins - metabolism
RNA, Messenger - metabolism
Sequence Homology, Amino Acid
Tissue Distribution
Transfection
Vesicular Transport Proteins
ISSN:0021-9258
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Description
Summary:The glycosaminoglycan hyaluronan is a key substrate for cell migration in tissues during inflammation, wound healing, and neoplasia. Unlike other matrix components, hyaluronan (HA) is turned over rapidly, yet most degradation occurs not locally but within distant lymph nodes, through mechanisms that are not yet understood. While it is not clear which receptors are involved in binding and uptake of hyaluronan within the lymphatics, one likely candidate is the lymphatic endothelial hyaluronan receptor LYVE-1 recently described in our laboratory (Banerji, S., Ni, J., Wang, S., Clasper, S., Su, J., Tammi, R., Jones, M., and Jackson, D.G. (1999) J. Cell Biol. 144, 789-801). Here we present evidence that LYVE-1 is involved in the uptake of hyaluronan by lymphatic endothelial cells using a new murine LYVE-1 orthologue identified from the EST data base. We show that mouse LYVE-1 both binds and internalizes hyaluronan in transfected 293T fibroblasts in vitro and demonstrate using immunoelectron microscopy that it is distributed equally among the luminal and abluminal surfaces of lymphatic vessels in vivo. In addition, we show by means of specific antisera that expression of mouse LYVE-1 remains restricted to the lymphatics in homozygous knockout mice lacking a functional gene for CD44, the closest homologue of LYVE-1 and the only other Link superfamily HA receptor known to date. Together these results suggest a role for LYVE-1 in the transport of HA from tissue to lymph and imply that further novel hyaluronan receptors must exist that can compensate for the loss of CD44 function.
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ISSN:0021-9258
DOI:10.1074/jbc.m011004200