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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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Nucleotide sequence and derived  amino acid sequence of LYVE-1, a novel human  HA receptor. A shows the complete nucleotide  and derived amino acid sequence for the 2,313-bp LYVE-1 cDNA clone in pBluescript. A  cleavable NH2-terminal leader predicted using  the −3 +1 rule (56) and a probable transmembrane anchor are underlined. The positions of  two putative N-glycosylation sites (N X S/T) are  boxed. The sequence predicts a 322–amino acid  residue polypeptide with a 26-residue leader  peptide, a 21-residue hydrophobic membrane  anchor, and a 63-residue cytoplasmic tail. B depicts Kyte-Doolittle (solid line) and Goldman  (stippled line) hydropathy plots of the derived  amino acid sequence, both of which confirm the  position of the predicted hydrophobic transmembrane anchor. These sequence data are  available from GenBank under accession number AF118108.
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Figure 1: Nucleotide sequence and derived amino acid sequence of LYVE-1, a novel human HA receptor. A shows the complete nucleotide and derived amino acid sequence for the 2,313-bp LYVE-1 cDNA clone in pBluescript. A cleavable NH2-terminal leader predicted using the −3 +1 rule (56) and a probable transmembrane anchor are underlined. The positions of two putative N-glycosylation sites (N X S/T) are boxed. The sequence predicts a 322–amino acid residue polypeptide with a 26-residue leader peptide, a 21-residue hydrophobic membrane anchor, and a 63-residue cytoplasmic tail. B depicts Kyte-Doolittle (solid line) and Goldman (stippled line) hydropathy plots of the derived amino acid sequence, both of which confirm the position of the predicted hydrophobic transmembrane anchor. These sequence data are available from GenBank under accession number AF118108.

Mentions: To identify new HA receptors we searched recent databases of ESTs for cDNAs homologous to the CD44 molecule, currently thought to be the primary HA receptor on mammalian cells. A homology search of the combined Human Genome Sciences/TIGR EST databases with the amino acid sequence of full-length CD44H using the BLAST program identified a number of ESTs with predicted amino acid sequences >30% similar to CD44. 59 identical ESTs were identified in libraries prepared from fetal tissues including liver, spleen, brain, and heart; adult human placenta, bone marrow, lung, and spinal cord; glioblastoma, ovarian, and bone tumor; and HUVEC. The 2,313-bp EST from HUVEC which we have termed LYVE-1 (lymphatic vessel endothelial HA receptor) was subjected to complete nucleotide sequencing. Translation of the LYVE-1 cDNA (Fig. 1 A) revealed a large (966 bp) open reading frame starting with a Kozak (24) consensus ATG initiation codon at position 91 and terminating with the TAG stop codon at position 1057. The deduced amino acid sequence encodes a 322-residue polypeptide with the features characteristic of a type I integral membrane glycoprotein. These are: a sequence of 26 largely hydrophobic residues at the NH2 terminus most likely comprising the leader peptide; a hydrophilic sequence of 212 amino acids containing seven cysteine residues, a serine/threonine-rich region (residues 145–216) and two motifs for N-linked glycosylation (NFT and NSS, centered on residues 54 and 131, respectively) corresponding to an extracellular domain; a sequence of 21 hydrophobic residues immediately followed by the dibasic motif KR and a highly charged stretch of 63 residues predicted to form the transmembrane anchor and cytoplasmic tail, respectively (Fig. 1 A). The predicted transmembrane anchor is also apparent in Kyte-Doolittle (25) and Goldman hydropathy plots of the deduced amino acid sequence (Fig. 1 B). The position of the mature NH2 terminus is predicted to be Ala 27 based on the −3 +1 rule proposed by Von Heijne (56).


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)

Nucleotide sequence and derived  amino acid sequence of LYVE-1, a novel human  HA receptor. A shows the complete nucleotide  and derived amino acid sequence for the 2,313-bp LYVE-1 cDNA clone in pBluescript. A  cleavable NH2-terminal leader predicted using  the −3 +1 rule (56) and a probable transmembrane anchor are underlined. The positions of  two putative N-glycosylation sites (N X S/T) are  boxed. The sequence predicts a 322–amino acid  residue polypeptide with a 26-residue leader  peptide, a 21-residue hydrophobic membrane  anchor, and a 63-residue cytoplasmic tail. B depicts Kyte-Doolittle (solid line) and Goldman  (stippled line) hydropathy plots of the derived  amino acid sequence, both of which confirm the  position of the predicted hydrophobic transmembrane anchor. These sequence data are  available from GenBank under accession number AF118108.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2132933&req=5

Figure 1: Nucleotide sequence and derived amino acid sequence of LYVE-1, a novel human HA receptor. A shows the complete nucleotide and derived amino acid sequence for the 2,313-bp LYVE-1 cDNA clone in pBluescript. A cleavable NH2-terminal leader predicted using the −3 +1 rule (56) and a probable transmembrane anchor are underlined. The positions of two putative N-glycosylation sites (N X S/T) are boxed. The sequence predicts a 322–amino acid residue polypeptide with a 26-residue leader peptide, a 21-residue hydrophobic membrane anchor, and a 63-residue cytoplasmic tail. B depicts Kyte-Doolittle (solid line) and Goldman (stippled line) hydropathy plots of the derived amino acid sequence, both of which confirm the position of the predicted hydrophobic transmembrane anchor. These sequence data are available from GenBank under accession number AF118108.
Mentions: To identify new HA receptors we searched recent databases of ESTs for cDNAs homologous to the CD44 molecule, currently thought to be the primary HA receptor on mammalian cells. A homology search of the combined Human Genome Sciences/TIGR EST databases with the amino acid sequence of full-length CD44H using the BLAST program identified a number of ESTs with predicted amino acid sequences >30% similar to CD44. 59 identical ESTs were identified in libraries prepared from fetal tissues including liver, spleen, brain, and heart; adult human placenta, bone marrow, lung, and spinal cord; glioblastoma, ovarian, and bone tumor; and HUVEC. The 2,313-bp EST from HUVEC which we have termed LYVE-1 (lymphatic vessel endothelial HA receptor) was subjected to complete nucleotide sequencing. Translation of the LYVE-1 cDNA (Fig. 1 A) revealed a large (966 bp) open reading frame starting with a Kozak (24) consensus ATG initiation codon at position 91 and terminating with the TAG stop codon at position 1057. The deduced amino acid sequence encodes a 322-residue polypeptide with the features characteristic of a type I integral membrane glycoprotein. These are: a sequence of 26 largely hydrophobic residues at the NH2 terminus most likely comprising the leader peptide; a hydrophilic sequence of 212 amino acids containing seven cysteine residues, a serine/threonine-rich region (residues 145–216) and two motifs for N-linked glycosylation (NFT and NSS, centered on residues 54 and 131, respectively) corresponding to an extracellular domain; a sequence of 21 hydrophobic residues immediately followed by the dibasic motif KR and a highly charged stretch of 63 residues predicted to form the transmembrane anchor and cytoplasmic tail, respectively (Fig. 1 A). The predicted transmembrane anchor is also apparent in Kyte-Doolittle (25) and Goldman hydropathy plots of the deduced amino acid sequence (Fig. 1 B). The position of the mature NH2 terminus is predicted to be Ala 27 based on the −3 +1 rule proposed by Von Heijne (56).

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