Studies on structures and functions of fungus glycolipid-metabolizing enzymes

2014 Fiscal Year Final Research Report

• Project/Area Number: 24380058
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Applied biochemistry
• Research Institution: Kyushu University
• Principal Investigator: ITO Makoto 九州大学, (連合)農学研究科(研究院), 教授 (40253512)
• Co-Investigator(Kenkyū-buntansha): 角田 佳充 九州大学, 大学院農学研究院, 准教授 (00314360) ; 沖野 望 九州大学, 大学院農学研究院, 准教授 (90363324)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 糖脂質 / 代謝 / 分解酵素 / 真菌類 / グルコシルセラミド / ステリルグルコシド / 液胞形成

Outline of Final Research Achievements

The two major glycolipids in C. neoformans are glucosylceramide (GlcCer) and steryl β-glucoside (SG). We found two homologues of EGCase in C. neoformans and designated EGCrP1 and EGCrP2. EGCrP1 is a neutral glucocerebrosidase specific to GlcCer, whereas EGCrP2 is an acid β-glucosidase capable of hydrolyzing not only GlcCer but also various β-glucosides, including SG. Using each disruption mutant of egcrp1 and egcrp2, we elucidated that EGCrP1 plays an integral role in quality control of the fungus specific GlcCer, whereas EGCrP2 is involved in the catabolism of SG in the vacuoles of C. neoformans. The disruption of EG catabolism resulted in growth arrest, dysfunction in cell budding, and abnormal vacuole morphology. These results indicate that catabolism of two different glycolipids plays different physiological roles in C. neoformans and strongly suggest EGCrP1 and EGCrP2 as targets for anti-cryptococcal drugs with a new mechanism of action.

Free Research Field

生化学