The gene defective in leukocyte adhesion deficiency II encodes a putative GDP-fucose transporter.
Leukocyte adhesion deficiency II (LAD II) is characterized by the lack of fucosylated glycoconjugates, including selectin ligands, causing immunodeficiency and severe mental and growth retardation. No deficiency in fucosyltransferase activities or in the activities of enzymes involved in GDP-fucose...
| Main Authors: | , , , , |
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| Format: | Journal article |
| Language: | English |
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2001
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| _version_ | 1826261681933647872 |
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| author | Lühn, K Wild, M Eckhardt, M Gerardy-Schahn, R Vestweber, D |
| author_facet | Lühn, K Wild, M Eckhardt, M Gerardy-Schahn, R Vestweber, D |
| author_sort | Lühn, K |
| collection | OXFORD |
| description | Leukocyte adhesion deficiency II (LAD II) is characterized by the lack of fucosylated glycoconjugates, including selectin ligands, causing immunodeficiency and severe mental and growth retardation. No deficiency in fucosyltransferase activities or in the activities of enzymes involved in GDP-fucose biosynthesis has been found. Instead, the transport of GDP-fucose into isolated Golgi vesicles of LAD II cells appeared to be reduced. To identify the gene mutated in LAD II, we cloned 12 cDNAs from Caenorhabditis elegans, encoding multi-spanning transmembrane proteins with homology to known nucleotide sugar transporters, and transfected them into fibroblasts from an LAD II patient. One of these clones re-established expression of fucosylated glycoconjugates with high efficiency and allowed us to identify a human homolog with 55% identity, which also directed re-expression of fucosylated glycoconjugates. Both proteins were localized to the Golgi. The corresponding endogenous protein in LAD II cells had an R147C amino acid change in the conserved fourth transmembrane region. Overexpression of this mutant protein in cells from a patient with LAD II did not rescue fucosylation, demonstrating that the point mutation affected the activity of the protein. Thus, we have identified the first putative GDP-fucose transporter, which has been highly conserved throughout evolution. A point mutation in its gene is responsible for the disease in this patient with LAD II. |
| first_indexed | 2024-03-06T19:25:10Z |
| format | Journal article |
| id | oxford-uuid:1b73661a-ebd0-415e-99a0-9be258e777b0 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T19:25:10Z |
| publishDate | 2001 |
| record_format | dspace |
| spelling | oxford-uuid:1b73661a-ebd0-415e-99a0-9be258e777b02022-03-26T11:00:28ZThe gene defective in leukocyte adhesion deficiency II encodes a putative GDP-fucose transporter.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:1b73661a-ebd0-415e-99a0-9be258e777b0EnglishSymplectic Elements at Oxford2001Lühn, KWild, MEckhardt, MGerardy-Schahn, RVestweber, DLeukocyte adhesion deficiency II (LAD II) is characterized by the lack of fucosylated glycoconjugates, including selectin ligands, causing immunodeficiency and severe mental and growth retardation. No deficiency in fucosyltransferase activities or in the activities of enzymes involved in GDP-fucose biosynthesis has been found. Instead, the transport of GDP-fucose into isolated Golgi vesicles of LAD II cells appeared to be reduced. To identify the gene mutated in LAD II, we cloned 12 cDNAs from Caenorhabditis elegans, encoding multi-spanning transmembrane proteins with homology to known nucleotide sugar transporters, and transfected them into fibroblasts from an LAD II patient. One of these clones re-established expression of fucosylated glycoconjugates with high efficiency and allowed us to identify a human homolog with 55% identity, which also directed re-expression of fucosylated glycoconjugates. Both proteins were localized to the Golgi. The corresponding endogenous protein in LAD II cells had an R147C amino acid change in the conserved fourth transmembrane region. Overexpression of this mutant protein in cells from a patient with LAD II did not rescue fucosylation, demonstrating that the point mutation affected the activity of the protein. Thus, we have identified the first putative GDP-fucose transporter, which has been highly conserved throughout evolution. A point mutation in its gene is responsible for the disease in this patient with LAD II. |
| spellingShingle | Lühn, K Wild, M Eckhardt, M Gerardy-Schahn, R Vestweber, D The gene defective in leukocyte adhesion deficiency II encodes a putative GDP-fucose transporter. |
| title | The gene defective in leukocyte adhesion deficiency II encodes a putative GDP-fucose transporter. |
| title_full | The gene defective in leukocyte adhesion deficiency II encodes a putative GDP-fucose transporter. |
| title_fullStr | The gene defective in leukocyte adhesion deficiency II encodes a putative GDP-fucose transporter. |
| title_full_unstemmed | The gene defective in leukocyte adhesion deficiency II encodes a putative GDP-fucose transporter. |
| title_short | The gene defective in leukocyte adhesion deficiency II encodes a putative GDP-fucose transporter. |
| title_sort | gene defective in leukocyte adhesion deficiency ii encodes a putative gdp fucose transporter |
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