Novel Insights into Selected Disease-Causing Mutations within the <i>SLC35A1</i> Gene Encoding the CMP-Sialic Acid Transporter
Congenital disorders of glycosylation (CDG) are a group of rare genetic and metabolic diseases caused by alterations in glycosylation pathways. Five patients bearing CDG-causing mutations in the <i>SLC35A1</i> gene encoding the CMP-sialic acid transporter (CST) have been reported to date...
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MDPI AG
2020-12-01
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| Series: | International Journal of Molecular Sciences |
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| author | Bożena Szulc Yelyzaveta Zadorozhna Mariusz Olczak Wojciech Wiertelak Dorota Maszczak-Seneczko |
| author_facet | Bożena Szulc Yelyzaveta Zadorozhna Mariusz Olczak Wojciech Wiertelak Dorota Maszczak-Seneczko |
| author_sort | Bożena Szulc |
| collection | DOAJ |
| description | Congenital disorders of glycosylation (CDG) are a group of rare genetic and metabolic diseases caused by alterations in glycosylation pathways. Five patients bearing CDG-causing mutations in the <i>SLC35A1</i> gene encoding the CMP-sialic acid transporter (CST) have been reported to date. In this study we examined how specific mutations in the <i>SLC35A1</i> gene affect the protein’s properties in two previously described SLC35A1-CDG cases: one caused by a substitution (Q101H) and another involving a compound heterozygous mutation (T156R/E196K). The effects of single mutations and the combination of T156R and E196K mutations on the CST’s functionality was examined separately in CST-deficient HEK293T cells. As shown by microscopic studies, none of the CDG-causing mutations affected the protein’s proper localization in the Golgi apparatus. Cellular glycophenotypes were characterized using lectins, structural assignment of N- and O-glycans and analysis of glycolipids. Single Q101H, T156R and E196K mutants were able to partially restore sialylation in CST-deficient cells, and the deleterious effect of a single T156R or E196K mutation on the CST functionality was strongly enhanced upon their combination. We also revealed differences in the ability of CST variants to form dimers. The results of this study improve our understanding of the molecular background of SLC35A1-CDG cases. |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T13:39:46Z |
| publishDate | 2020-12-01 |
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| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-7d95df8e55f641a599d68699b06a08c82023-11-21T03:07:08ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-12-0122130410.3390/ijms22010304Novel Insights into Selected Disease-Causing Mutations within the <i>SLC35A1</i> Gene Encoding the CMP-Sialic Acid TransporterBożena Szulc0Yelyzaveta Zadorozhna1Mariusz Olczak2Wojciech Wiertelak3Dorota Maszczak-Seneczko4Faculty of Biotechnology, University of Wroclaw, 14A F. Joliot-Curie St., 50-383 Wroclaw, PolandFaculty of Biotechnology, University of Wroclaw, 14A F. Joliot-Curie St., 50-383 Wroclaw, PolandFaculty of Biotechnology, University of Wroclaw, 14A F. Joliot-Curie St., 50-383 Wroclaw, PolandFaculty of Biotechnology, University of Wroclaw, 14A F. Joliot-Curie St., 50-383 Wroclaw, PolandFaculty of Biotechnology, University of Wroclaw, 14A F. Joliot-Curie St., 50-383 Wroclaw, PolandCongenital disorders of glycosylation (CDG) are a group of rare genetic and metabolic diseases caused by alterations in glycosylation pathways. Five patients bearing CDG-causing mutations in the <i>SLC35A1</i> gene encoding the CMP-sialic acid transporter (CST) have been reported to date. In this study we examined how specific mutations in the <i>SLC35A1</i> gene affect the protein’s properties in two previously described SLC35A1-CDG cases: one caused by a substitution (Q101H) and another involving a compound heterozygous mutation (T156R/E196K). The effects of single mutations and the combination of T156R and E196K mutations on the CST’s functionality was examined separately in CST-deficient HEK293T cells. As shown by microscopic studies, none of the CDG-causing mutations affected the protein’s proper localization in the Golgi apparatus. Cellular glycophenotypes were characterized using lectins, structural assignment of N- and O-glycans and analysis of glycolipids. Single Q101H, T156R and E196K mutants were able to partially restore sialylation in CST-deficient cells, and the deleterious effect of a single T156R or E196K mutation on the CST functionality was strongly enhanced upon their combination. We also revealed differences in the ability of CST variants to form dimers. The results of this study improve our understanding of the molecular background of SLC35A1-CDG cases.https://www.mdpi.com/1422-0067/22/1/304CMP-sialic acid transportersialylationcongenital disorder of glycosylationmutationGolgi apparatuslectin |
| spellingShingle | Bożena Szulc Yelyzaveta Zadorozhna Mariusz Olczak Wojciech Wiertelak Dorota Maszczak-Seneczko Novel Insights into Selected Disease-Causing Mutations within the <i>SLC35A1</i> Gene Encoding the CMP-Sialic Acid Transporter International Journal of Molecular Sciences CMP-sialic acid transporter sialylation congenital disorder of glycosylation mutation Golgi apparatus lectin |
| title | Novel Insights into Selected Disease-Causing Mutations within the <i>SLC35A1</i> Gene Encoding the CMP-Sialic Acid Transporter |
| title_full | Novel Insights into Selected Disease-Causing Mutations within the <i>SLC35A1</i> Gene Encoding the CMP-Sialic Acid Transporter |
| title_fullStr | Novel Insights into Selected Disease-Causing Mutations within the <i>SLC35A1</i> Gene Encoding the CMP-Sialic Acid Transporter |
| title_full_unstemmed | Novel Insights into Selected Disease-Causing Mutations within the <i>SLC35A1</i> Gene Encoding the CMP-Sialic Acid Transporter |
| title_short | Novel Insights into Selected Disease-Causing Mutations within the <i>SLC35A1</i> Gene Encoding the CMP-Sialic Acid Transporter |
| title_sort | novel insights into selected disease causing mutations within the i slc35a1 i gene encoding the cmp sialic acid transporter |
| topic | CMP-sialic acid transporter sialylation congenital disorder of glycosylation mutation Golgi apparatus lectin |
| url | https://www.mdpi.com/1422-0067/22/1/304 |
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