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Regulation of the Axillary Osmidrosis-Associated ABCC11 Protein Stability by N-Linked Glycosylation: Effect of Glucose Condition
ATP-binding cassette C11 (ABCC11) is a plasma membrane protein involved in the transport of a variety of lipophilic anions. ABCC11 wild-type is responsible for the high-secretion phenotypes in human apocrine glands, such as that of wet-type ear wax, and the risk of axillary osmidrosis. We have previ...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Public Library of Science
2016
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4900533/ https://www.ncbi.nlm.nih.gov/pubmed/27281343 http://dx.doi.org/10.1371/journal.pone.0157172 |
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author | Toyoda, Yu Takada, Tappei Miyata, Hiroshi Ishikawa, Toshihisa Suzuki, Hiroshi |
author_facet | Toyoda, Yu Takada, Tappei Miyata, Hiroshi Ishikawa, Toshihisa Suzuki, Hiroshi |
author_sort | Toyoda, Yu |
collection | PubMed |
description | ATP-binding cassette C11 (ABCC11) is a plasma membrane protein involved in the transport of a variety of lipophilic anions. ABCC11 wild-type is responsible for the high-secretion phenotypes in human apocrine glands, such as that of wet-type ear wax, and the risk of axillary osmidrosis. We have previously reported that mature ABCC11 is a glycoprotein containing two N-linked glycans at Asn838 and Asn844. However, little is known about the role of N-linked glycosylation in the regulation of ABCC11 protein. In the current study, we investigated the effects of N-linked glycosylation on the protein level and localization of ABCC11 using polarized Madin-Darby canine kidney II cells. When the N-linked glycosylation in ABCC11-expressing cells was chemically inhibited by tunicamycin treatment, the maturation of ABCC11 was suppressed and its protein level was significantly decreased. Immunoblotting analyses demonstrated that the protein level of the N-linked glycosylation-deficient mutant (N838Q and N844Q: Q838/844) was about half of the ABCC11 wild-type level. Further biochemical studies with the Q838/844 mutant showed that this glycosylation-deficient ABCC11 was degraded faster than wild-type probably due to the enhancement of the MG132-sensitive protein degradation pathway. Moreover, the incubation of ABCC11 wild-type-expressing cells in a low-glucose condition decreased mature, glycosylated ABCC11, compared with the high-glucose condition. On the other hand, the protein level of the Q838/844 mutant was not affected by glucose condition. These results suggest that N-linked glycosylation is important for the protein stability of ABCC11, and physiological alteration in glucose may affect the ABCC11 protein level and ABCC11-related phenotypes in humans, such as axillary osmidrosis. |
format | Online Article Text |
id | pubmed-4900533 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-49005332016-06-24 Regulation of the Axillary Osmidrosis-Associated ABCC11 Protein Stability by N-Linked Glycosylation: Effect of Glucose Condition Toyoda, Yu Takada, Tappei Miyata, Hiroshi Ishikawa, Toshihisa Suzuki, Hiroshi PLoS One Research Article ATP-binding cassette C11 (ABCC11) is a plasma membrane protein involved in the transport of a variety of lipophilic anions. ABCC11 wild-type is responsible for the high-secretion phenotypes in human apocrine glands, such as that of wet-type ear wax, and the risk of axillary osmidrosis. We have previously reported that mature ABCC11 is a glycoprotein containing two N-linked glycans at Asn838 and Asn844. However, little is known about the role of N-linked glycosylation in the regulation of ABCC11 protein. In the current study, we investigated the effects of N-linked glycosylation on the protein level and localization of ABCC11 using polarized Madin-Darby canine kidney II cells. When the N-linked glycosylation in ABCC11-expressing cells was chemically inhibited by tunicamycin treatment, the maturation of ABCC11 was suppressed and its protein level was significantly decreased. Immunoblotting analyses demonstrated that the protein level of the N-linked glycosylation-deficient mutant (N838Q and N844Q: Q838/844) was about half of the ABCC11 wild-type level. Further biochemical studies with the Q838/844 mutant showed that this glycosylation-deficient ABCC11 was degraded faster than wild-type probably due to the enhancement of the MG132-sensitive protein degradation pathway. Moreover, the incubation of ABCC11 wild-type-expressing cells in a low-glucose condition decreased mature, glycosylated ABCC11, compared with the high-glucose condition. On the other hand, the protein level of the Q838/844 mutant was not affected by glucose condition. These results suggest that N-linked glycosylation is important for the protein stability of ABCC11, and physiological alteration in glucose may affect the ABCC11 protein level and ABCC11-related phenotypes in humans, such as axillary osmidrosis. Public Library of Science 2016-06-09 /pmc/articles/PMC4900533/ /pubmed/27281343 http://dx.doi.org/10.1371/journal.pone.0157172 Text en © 2016 Toyoda et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Toyoda, Yu Takada, Tappei Miyata, Hiroshi Ishikawa, Toshihisa Suzuki, Hiroshi Regulation of the Axillary Osmidrosis-Associated ABCC11 Protein Stability by N-Linked Glycosylation: Effect of Glucose Condition |
title | Regulation of the Axillary Osmidrosis-Associated ABCC11 Protein Stability by N-Linked Glycosylation: Effect of Glucose Condition |
title_full | Regulation of the Axillary Osmidrosis-Associated ABCC11 Protein Stability by N-Linked Glycosylation: Effect of Glucose Condition |
title_fullStr | Regulation of the Axillary Osmidrosis-Associated ABCC11 Protein Stability by N-Linked Glycosylation: Effect of Glucose Condition |
title_full_unstemmed | Regulation of the Axillary Osmidrosis-Associated ABCC11 Protein Stability by N-Linked Glycosylation: Effect of Glucose Condition |
title_short | Regulation of the Axillary Osmidrosis-Associated ABCC11 Protein Stability by N-Linked Glycosylation: Effect of Glucose Condition |
title_sort | regulation of the axillary osmidrosis-associated abcc11 protein stability by n-linked glycosylation: effect of glucose condition |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4900533/ https://www.ncbi.nlm.nih.gov/pubmed/27281343 http://dx.doi.org/10.1371/journal.pone.0157172 |
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