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LYVE-1, a new homologue of the CD44 glycoprotein, is a lymph-specific receptor for hyaluronan.

Banerji S, Ni J, Wang SX, Clasper S, Su J, Tammi R, Jones M, Jackson DG - J. Cell Biol. (1999)

Bottom Line: Like CD44, the LYVE-1 molecule binds both soluble and immobilized HA.However, unlike CD44, the LYVE-1 molecule colocalizes with HA on the luminal face of the lymph vessel wall and is completely absent from blood vessels.Hence, LYVE-1 is the first lymph-specific HA receptor to be characterized and is a uniquely powerful marker for lymph vessels themselves.

View Article: PubMed Central - PubMed

Affiliation: University of Oxford, Molecular Immunology Group, Nuffield Department of Medicine, John Radcliff Hospital, Headington, Oxford OX3 9DU, United Kingdom.

ABSTRACT
The extracellular matrix glycosaminoglycan hyaluronan (HA) is an abundant component of skin and mesenchymal tissues where it facilitates cell migration during wound healing, inflammation, and embryonic morphogenesis. Both during normal tissue homeostasis and particularly after tissue injury, HA is mobilized from these sites through lymphatic vessels to the lymph nodes where it is degraded before entering the circulation for rapid uptake by the liver. Currently, however, the identities of HA binding molecules which control this pathway are unknown. Here we describe the first such molecule, LYVE-1, which we have identified as a major receptor for HA on the lymph vessel wall. The deduced amino acid sequence of LYVE-1 predicts a 322-residue type I integral membrane polypeptide 41% similar to the CD44 HA receptor with a 212-residue extracellular domain containing a single Link module the prototypic HA binding domain of the Link protein superfamily. Like CD44, the LYVE-1 molecule binds both soluble and immobilized HA. However, unlike CD44, the LYVE-1 molecule colocalizes with HA on the luminal face of the lymph vessel wall and is completely absent from blood vessels. Hence, LYVE-1 is the first lymph-specific HA receptor to be characterized and is a uniquely powerful marker for lymph vessels themselves.

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Comparison of the LYVE-1 receptor Link module with  other Link superfamily members. In A, the derived amino acid  sequence of LYVE-1 (top line) is shown aligned with that of the  full-length human CD44 cDNA (bottom line) using the GCG  program GAP. Positions where amino acid residues are identical  are depicted with a line; semiconservative and conservative differences are depicted with one or two dots, respectively. The two  sequences have an overall similarity of 41% and a similarity of  57% within the immediate Link homology unit (LYVE-1 residues 61–128). B shows a Prettyplot (GCG) comparison of sequence encompassing the “Link modules” (HA-binding domains) from LYVE-1 (corresponding to residues 40–138 in A),  human CD44, the soluble human tumor necrosis factor–inducible  TSG-6 molecule, and both tandem repeats (Links 1 and 2) of human Aggrecan, human Versican, and human Cartilage Link protein.
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Figure 2: Comparison of the LYVE-1 receptor Link module with other Link superfamily members. In A, the derived amino acid sequence of LYVE-1 (top line) is shown aligned with that of the full-length human CD44 cDNA (bottom line) using the GCG program GAP. Positions where amino acid residues are identical are depicted with a line; semiconservative and conservative differences are depicted with one or two dots, respectively. The two sequences have an overall similarity of 41% and a similarity of 57% within the immediate Link homology unit (LYVE-1 residues 61–128). B shows a Prettyplot (GCG) comparison of sequence encompassing the “Link modules” (HA-binding domains) from LYVE-1 (corresponding to residues 40–138 in A), human CD44, the soluble human tumor necrosis factor–inducible TSG-6 molecule, and both tandem repeats (Links 1 and 2) of human Aggrecan, human Versican, and human Cartilage Link protein.

Mentions: Alignment of the LYVE-1 amino acid sequence with that of the human CD44 HA receptor (Fig. 2) illustrates the degree of homology between the two molecules which have an overall similarity of 41%. Closer inspection reveals the region of maximal homology (57% similarity, 38% identity) to be contained within the area encompassing the extended CD44 Link domain and the corresponding region (residues 36–139) in the LYVE-1 sequence (Fig. 2 A). The location of the putative Link module in LYVE-1 is marked by four central cysteine residues (Cys 61, 85, 106, and 128), whose spacing (C1 - X23 - C2 - X20 - C3 - X20 - C4) is almost identical in CD44, and whose intervening sequences share 57% similarity. This similarity rises to 68% (57% identity) between C2 (Cys 85) and C3 (Cys 106). These four cysteine residues are conserved in all members of the Link superfamily where they form essential disulfide bridges that stabilize the HA-binding domain, a structure comprising two α helices and two anti–parallel β sheets surrounding a large hydrophobic core (23). Interestingly the two additional cysteine residues Cys 31 and Cys 133 that uniquely flank the CD44 Link module (13, 45) are also present at appropriately conserved locations in the LYVE-1 sequence (Cys 36 and Cys 139, Fig. 2 A). Downstream of the Link module, however, the region corresponding to the membrane proximal domain of LYVE-1 shows little similarity to CD44, with the exception of a moderately high proportion of serine and threonine residues (37% within residues 145–216).


LYVE-1, a new homologue of the CD44 glycoprotein, is a lymph-specific receptor for hyaluronan.

Banerji S, Ni J, Wang SX, Clasper S, Su J, Tammi R, Jones M, Jackson DG - J. Cell Biol. (1999)

Comparison of the LYVE-1 receptor Link module with  other Link superfamily members. In A, the derived amino acid  sequence of LYVE-1 (top line) is shown aligned with that of the  full-length human CD44 cDNA (bottom line) using the GCG  program GAP. Positions where amino acid residues are identical  are depicted with a line; semiconservative and conservative differences are depicted with one or two dots, respectively. The two  sequences have an overall similarity of 41% and a similarity of  57% within the immediate Link homology unit (LYVE-1 residues 61–128). B shows a Prettyplot (GCG) comparison of sequence encompassing the “Link modules” (HA-binding domains) from LYVE-1 (corresponding to residues 40–138 in A),  human CD44, the soluble human tumor necrosis factor–inducible  TSG-6 molecule, and both tandem repeats (Links 1 and 2) of human Aggrecan, human Versican, and human Cartilage Link protein.
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Related In: Results  -  Collection

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Figure 2: Comparison of the LYVE-1 receptor Link module with other Link superfamily members. In A, the derived amino acid sequence of LYVE-1 (top line) is shown aligned with that of the full-length human CD44 cDNA (bottom line) using the GCG program GAP. Positions where amino acid residues are identical are depicted with a line; semiconservative and conservative differences are depicted with one or two dots, respectively. The two sequences have an overall similarity of 41% and a similarity of 57% within the immediate Link homology unit (LYVE-1 residues 61–128). B shows a Prettyplot (GCG) comparison of sequence encompassing the “Link modules” (HA-binding domains) from LYVE-1 (corresponding to residues 40–138 in A), human CD44, the soluble human tumor necrosis factor–inducible TSG-6 molecule, and both tandem repeats (Links 1 and 2) of human Aggrecan, human Versican, and human Cartilage Link protein.
Mentions: Alignment of the LYVE-1 amino acid sequence with that of the human CD44 HA receptor (Fig. 2) illustrates the degree of homology between the two molecules which have an overall similarity of 41%. Closer inspection reveals the region of maximal homology (57% similarity, 38% identity) to be contained within the area encompassing the extended CD44 Link domain and the corresponding region (residues 36–139) in the LYVE-1 sequence (Fig. 2 A). The location of the putative Link module in LYVE-1 is marked by four central cysteine residues (Cys 61, 85, 106, and 128), whose spacing (C1 - X23 - C2 - X20 - C3 - X20 - C4) is almost identical in CD44, and whose intervening sequences share 57% similarity. This similarity rises to 68% (57% identity) between C2 (Cys 85) and C3 (Cys 106). These four cysteine residues are conserved in all members of the Link superfamily where they form essential disulfide bridges that stabilize the HA-binding domain, a structure comprising two α helices and two anti–parallel β sheets surrounding a large hydrophobic core (23). Interestingly the two additional cysteine residues Cys 31 and Cys 133 that uniquely flank the CD44 Link module (13, 45) are also present at appropriately conserved locations in the LYVE-1 sequence (Cys 36 and Cys 139, Fig. 2 A). Downstream of the Link module, however, the region corresponding to the membrane proximal domain of LYVE-1 shows little similarity to CD44, with the exception of a moderately high proportion of serine and threonine residues (37% within residues 145–216).

Bottom Line: Like CD44, the LYVE-1 molecule binds both soluble and immobilized HA.However, unlike CD44, the LYVE-1 molecule colocalizes with HA on the luminal face of the lymph vessel wall and is completely absent from blood vessels.Hence, LYVE-1 is the first lymph-specific HA receptor to be characterized and is a uniquely powerful marker for lymph vessels themselves.

View Article: PubMed Central - PubMed

Affiliation: University of Oxford, Molecular Immunology Group, Nuffield Department of Medicine, John Radcliff Hospital, Headington, Oxford OX3 9DU, United Kingdom.

ABSTRACT
The extracellular matrix glycosaminoglycan hyaluronan (HA) is an abundant component of skin and mesenchymal tissues where it facilitates cell migration during wound healing, inflammation, and embryonic morphogenesis. Both during normal tissue homeostasis and particularly after tissue injury, HA is mobilized from these sites through lymphatic vessels to the lymph nodes where it is degraded before entering the circulation for rapid uptake by the liver. Currently, however, the identities of HA binding molecules which control this pathway are unknown. Here we describe the first such molecule, LYVE-1, which we have identified as a major receptor for HA on the lymph vessel wall. The deduced amino acid sequence of LYVE-1 predicts a 322-residue type I integral membrane polypeptide 41% similar to the CD44 HA receptor with a 212-residue extracellular domain containing a single Link module the prototypic HA binding domain of the Link protein superfamily. Like CD44, the LYVE-1 molecule binds both soluble and immobilized HA. However, unlike CD44, the LYVE-1 molecule colocalizes with HA on the luminal face of the lymph vessel wall and is completely absent from blood vessels. Hence, LYVE-1 is the first lymph-specific HA receptor to be characterized and is a uniquely powerful marker for lymph vessels themselves.

Show MeSH
Related in: MedlinePlus