| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Goda, Hatsumi M. Taguchi, Ryo Okino, Nozomu Ikeda, Kazutaka Watanabe, Takashi Miyamoto, Tomofumi Ito, Tomoharu Ito, Makoto Ishibashi, Yohei |
| Description |
Author Affiliation: Watanabe T ( From the Department of Bioscience and Biotechnology, Graduate School of Bioresource and Bioenvironmental Sciences, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581, Japan.); Ito T ( From the Department of Bioscience and Biotechnology, Graduate School of Bioresource and Bioenvironmental Sciences, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581, Japan.); Goda HM ( From the Department of Bioscience and Biotechnology, Graduate School of Bioresource and Bioenvironmental Sciences, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581, Japan.); Ishibashi Y ( From the Department of Bioscience and Biotechnology, Graduate School of Bioresource and Bioenvironmental Sciences, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581, Japan.); Miyamoto T ( the Graduate School of Pharmaceutical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka 812-8582, Japan.); Ikeda K ( the Institute for Advanced Biosciences, Keio University, 246-2 Mizukami, Kakuganji, Tsuruoka, Yamagata 997-0052, Japan, and.); Taguchi R ( the Department of Biomedical Sciences, College of Life and Health Sciences, Chubu University, 1200 Matsumoto-cho, Kasugai-shi, Aichi 487-8501, Japan.); Okino N ( From the Department of Bioscience and Biotechnology, Graduate School of Bioresource and Bioenvironmental Sciences, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581, Japan.); Ito M ( From the Department of Bioscience and Biotechnology, Graduate School of Bioresource and Bioenvironmental Sciences, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581, Japan, makotoi@agr.kyushu-u.ac.jp.) |
| Abstract |
Cryptococcosis is an infectious disease caused by pathogenic fungi, such as Cryptococcus neoformans and Cryptococcus gattii. The ceramide structure (methyl-d18:2/h18:0) of C. neoformans glucosylceramide (GlcCer) is characteristic and strongly related to its pathogenicity. We recently identified endoglycoceramidase-related protein 1 (EGCrP1) as a glucocerebrosidase in C. neoformans and showed that it was involved in the quality control of GlcCer by eliminating immature GlcCer during the synthesis of GlcCer (Ishibashi, Y., Ikeda, K., Sakaguchi, K., Okino, N., Taguchi, R., and Ito, M. (2012) Quality control of fungus-specific glucosylceramide in Cryptococcus neoformans by endoglycoceramidase-related protein 1 (EGCrP1). J. Biol. Chem. 287, 368-381). We herein identified and characterized EGCrP2, a homologue of EGCrP1, as the enzyme responsible for sterylglucoside catabolism in C. neoformans. In contrast to EGCrP1, which is specific to GlcCer, EGCrP2 hydrolyzed various ß-glucosides, including GlcCer, cholesteryl-ß-glucoside, ergosteryl-ß-glucoside, sitosteryl-ß-glucoside, and para-nitrophenyl-ß-glucoside, but not -glucosides or ß-galactosides, under acidic conditions. Disruption of the EGCrP2 gene (egcrp2) resulted in the accumulation of a glycolipid, the structure of which was determined following purification to ergosteryl-3ß-glucoside, a major sterylglucoside in fungi, by mass spectrometric and two-dimensional nuclear magnetic resonance analyses. This glycolipid accumulated in vacuoles and EGCrP2 was detected in vacuole-enriched fraction. These results indicated that EGCrP2 was involved in the catabolism of ergosteryl-ß-glucoside in the vacuoles of C. neoformans. Distinct growth arrest, a dysfunction in cell budding, and an abnormal vacuole morphology were detected in the egcrp2-disrupted mutants, suggesting that EGCrP2 may be a promising target for anti-cryptococcal drugs. EGCrP2, classified into glycohydrolase family 5, is the first steryl-ß-glucosidase identified as well as a missing link in sterylglucoside metabolism in fungi. |
| ISSN |
00219258 |
| e-ISSN |
1083351X |
| Journal |
Journal of Biological Chemistry |
| Issue Number |
2 |
| Volume Number |
290 |
| Language |
English |
| Publisher |
American Society for Biochemistry and Molecular Biology (United States) |
| Publisher Date |
2015-01-09 |
| Publisher Place |
United States |
| Access Restriction |
Open |
| Subject Keyword |
Cellulases Genetics Ceramides Metabolism Cryptococcosis Enzymology Cryptococcus Neoformans Fungal Proteins Glycoside Hydrolases Chemistry Pathology Pathogenicity Glucosylceramides Glycolipids Research Support, Non-U.S. Gov't Biochemistry Molecular Biology |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Cell Biology Biochemistry Molecular Biology |
