| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
|
|---|
| Outline of Final Research Achievements |
In HEK cells stably expressing Niemann-Pick C1 Like 1 (NPC1L1)-YFP, overexpression of oxysterol-binding protein (OSBP)-related protein 10 (ORP10) increased the protein level of NPC1L1-YFP and enhanced cellular cholesterol uptake. The latter effect was more prominent with the ORP10 D254 isoform, which has been shown to predispose to hyper-LDL cholesterolemia, than with the N254 isoform. In reciprocal experiments, Co-immunoprecipitation (IP) assays showed that ORP10 interacted with both NPC1L1 and Numb via its N-terminal pleckstrin homology domain and C-terminal OSBP-related ligand-binding domain, respectively。Fluorescence resonance energy transfer (FRET) analyses revealed a clear difference in the intramolecular FRET efficacy between the two isoforms. These findings suggested that ORP10 regulates NPC1L1 internalization and that differential impact on NPC1L1-dependent cholesterol transport may underlie association of the D254 isoform with hyper-LDL cholesterolemia.
|
