| Project/Area Number |
22890237
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Single-year Grants |
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| Research Field |
General medical chemistry
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| Research Institution | The Institute of Physical and Chemical Research |
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Principal Investigator |
FUKUNAKA Ayako 独立行政法人理化学研究所, 複数分子イメージング研究チーム, 研究員 (60586402)
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| Project Period (FY) |
2010 – 2011
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| Project Status |
Completed (Fiscal Year 2011)
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| Budget Amount *help |
¥3,146,000 (Direct Cost: ¥2,420,000、Indirect Cost: ¥726,000)
Fiscal Year 2011: ¥1,508,000 (Direct Cost: ¥1,160,000、Indirect Cost: ¥348,000)
Fiscal Year 2010: ¥1,638,000 (Direct Cost: ¥1,260,000、Indirect Cost: ¥378,000)
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| Keywords | 亜鉛トランスポーター / 亜鉛要求性酵素 / 分泌経路 / 活性化機構 |
|---|
| Research Abstract |
The reduced activity of TNAP in DT40 cells deficient of two ZnT complexes(ZnT5/ZnT6 heterodimer and ZnT7 homo-oligomer) was not restored by zinc supplementation nor by exogenous expression of other ZnTs that increase the zinc content in the early secretory pathway. Moreover the expression of ZnT5/ZnT6 heterodimers reconstituted with zinc-transport-incompetent ZnT5 mutant failed to restore TNAP activity, but could stabilize the TNAP protein as the apo-form. These findings demonstrate that TNAP is activated not simply by passive zinc binding, but by an elaborate two-step mechanism via protein stabilization followed by enzyme conversion from the apo-to the holo-form with zinc loaded by ZnT complexes in the early secretory pathway.
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