| Budget Amount *help |
¥18,070,000 (Direct Cost: ¥13,900,000、Indirect Cost: ¥4,170,000)
Fiscal Year 2014: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2013: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2012: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
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| 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.
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