Histories of Dermatan Sulfate Epimerase and Dermatan 4-<i>O</i>-Sulfotransferase from Discovery of Their Enzymes and Genes to Musculocontractural Ehlers-Danlos Syndrome
Dermatan sulfate (DS) and its proteoglycans are essential for the assembly of the extracellular matrix and cell signaling. Various transporters and biosynthetic enzymes for nucleotide sugars, glycosyltransferases, epimerase, and sulfotransferases, are involved in the biosynthesis of DS. Among these...
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| Format: | Article |
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MDPI AG
2023-02-01
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| Series: | Genes |
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| Online Access: | https://www.mdpi.com/2073-4425/14/2/509 |
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| author | Shuji Mizumoto Shuhei Yamada |
| author_facet | Shuji Mizumoto Shuhei Yamada |
| author_sort | Shuji Mizumoto |
| collection | DOAJ |
| description | Dermatan sulfate (DS) and its proteoglycans are essential for the assembly of the extracellular matrix and cell signaling. Various transporters and biosynthetic enzymes for nucleotide sugars, glycosyltransferases, epimerase, and sulfotransferases, are involved in the biosynthesis of DS. Among these enzymes, dermatan sulfate epimerase (DSE) and dermatan 4-<i>O</i>-sulfotranserase (D4ST) are rate-limiting factors of DS biosynthesis. Pathogenic variants in human genes encoding DSE and D4ST cause the musculocontractural type of Ehlers-Danlos syndrome, characterized by tissue fragility, joint hypermobility, and skin hyperextensibility. DS-deficient mice exhibit perinatal lethality, myopathy-related phenotypes, thoracic kyphosis, vascular abnormalities, and skin fragility. These findings indicate that DS is essential for tissue development as well as homeostasis. This review focuses on the histories of DSE as well as D4ST, and their knockout mice as well as human congenital disorders. |
| first_indexed | 2024-03-11T08:47:21Z |
| format | Article |
| id | doaj.art-d7952334cb6b4e2e8e36a2530d5dc955 |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-11T08:47:21Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-d7952334cb6b4e2e8e36a2530d5dc9552023-11-16T20:43:57ZengMDPI AGGenes2073-44252023-02-0114250910.3390/genes14020509Histories of Dermatan Sulfate Epimerase and Dermatan 4-<i>O</i>-Sulfotransferase from Discovery of Their Enzymes and Genes to Musculocontractural Ehlers-Danlos SyndromeShuji Mizumoto0Shuhei Yamada1Department of Pathobiochemistry, Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya 468-8503, JapanDepartment of Pathobiochemistry, Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya 468-8503, JapanDermatan sulfate (DS) and its proteoglycans are essential for the assembly of the extracellular matrix and cell signaling. Various transporters and biosynthetic enzymes for nucleotide sugars, glycosyltransferases, epimerase, and sulfotransferases, are involved in the biosynthesis of DS. Among these enzymes, dermatan sulfate epimerase (DSE) and dermatan 4-<i>O</i>-sulfotranserase (D4ST) are rate-limiting factors of DS biosynthesis. Pathogenic variants in human genes encoding DSE and D4ST cause the musculocontractural type of Ehlers-Danlos syndrome, characterized by tissue fragility, joint hypermobility, and skin hyperextensibility. DS-deficient mice exhibit perinatal lethality, myopathy-related phenotypes, thoracic kyphosis, vascular abnormalities, and skin fragility. These findings indicate that DS is essential for tissue development as well as homeostasis. This review focuses on the histories of DSE as well as D4ST, and their knockout mice as well as human congenital disorders.https://www.mdpi.com/2073-4425/14/2/509chondroitin sulfatedermatan sulfatedermatan sulfate epimerasedermatan 4-<i>O</i>-sulfotransferaseEhlers-Danlos syndromeglycosaminoglycan |
| spellingShingle | Shuji Mizumoto Shuhei Yamada Histories of Dermatan Sulfate Epimerase and Dermatan 4-<i>O</i>-Sulfotransferase from Discovery of Their Enzymes and Genes to Musculocontractural Ehlers-Danlos Syndrome Genes chondroitin sulfate dermatan sulfate dermatan sulfate epimerase dermatan 4-<i>O</i>-sulfotransferase Ehlers-Danlos syndrome glycosaminoglycan |
| title | Histories of Dermatan Sulfate Epimerase and Dermatan 4-<i>O</i>-Sulfotransferase from Discovery of Their Enzymes and Genes to Musculocontractural Ehlers-Danlos Syndrome |
| title_full | Histories of Dermatan Sulfate Epimerase and Dermatan 4-<i>O</i>-Sulfotransferase from Discovery of Their Enzymes and Genes to Musculocontractural Ehlers-Danlos Syndrome |
| title_fullStr | Histories of Dermatan Sulfate Epimerase and Dermatan 4-<i>O</i>-Sulfotransferase from Discovery of Their Enzymes and Genes to Musculocontractural Ehlers-Danlos Syndrome |
| title_full_unstemmed | Histories of Dermatan Sulfate Epimerase and Dermatan 4-<i>O</i>-Sulfotransferase from Discovery of Their Enzymes and Genes to Musculocontractural Ehlers-Danlos Syndrome |
| title_short | Histories of Dermatan Sulfate Epimerase and Dermatan 4-<i>O</i>-Sulfotransferase from Discovery of Their Enzymes and Genes to Musculocontractural Ehlers-Danlos Syndrome |
| title_sort | histories of dermatan sulfate epimerase and dermatan 4 i o i sulfotransferase from discovery of their enzymes and genes to musculocontractural ehlers danlos syndrome |
| topic | chondroitin sulfate dermatan sulfate dermatan sulfate epimerase dermatan 4-<i>O</i>-sulfotransferase Ehlers-Danlos syndrome glycosaminoglycan |
| url | https://www.mdpi.com/2073-4425/14/2/509 |
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