Regulation of the dominant-negative-isoform of Ca^<2+>-activated K^+channel K_<Ca> 3.1 and its role in various diseases
| Project/Area Number |
21590098
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | Nagoya City University |
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Principal Investigator |
OHYA Susumu 名古屋市立大学, 大学院・薬学研究科, 准教授 (70275147)
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| Project Period (FY) |
2009 – 2011
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| Project Status |
Completed (Fiscal Year 2011)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2009: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 薬理学 / イオンチャネル / Tリンパ球 / アレルギー性疾患 / 炎症性疾患 / 転写調節 / Ca^<2+>活性化K^+チャネル / 転写抑制因子REST / 炎症性腸疾患 / K_<Ca>3.1阻害薬 / 前立腺肥大症 / 増殖性疾患 / スクリーニング / リンパ組織 / カルシウム活性化カリウムチャネル / 細胞増殖 / 転写調節因子 / 接触過敏症 / 胸腺細胞 / 白血病細胞株K562 / Ca^2+活性化K^+チャネル / ドミナントネガティブ / 巨核球 / 細胞分化誘導 / タンパク質相互作用 |
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| Research Abstract |
The novel spliced variant of intermediate-conductance Ca^<2+>-activated K^+channel K_<Ca> 3.1(K_<Ca> 3.1-sp/K_<Ca> 3.1b) has been identified from the human immune tissues, which were lacking the N-terminal domains of the original K_<Ca> 3.1a as a result of alternative splicing. The cellular distribution of CFP-tagged K_<Ca> 3.1a and/or YFP-tagged K_<Ca> 3.1-sp isoforms showed that K_<Ca> 3.1-sp suppressed the localization of K_<Ca> 3.1a to the plasma membrane, and co-expression of K_<Ca> 3.1-sp with K_<Ca> 3.1a suppressed IK_<Ca> channel activity of K_<Ca> 3.1a in a dominant-negative manner. In addition, the up-regulation and over-expression of K_<Ca> 3.1-sp suppressed thymocyte growth by down-regulation of IL-2 transcripts. These suggest that the N-terminal domain of K_<Ca> 3.1 is critical for channel trafficking to the plasma membrane, and that the fine tuning of IK_<Ca> channel activity modulated through alternative splicing may be related to the control in physiological and pathophysiological conditions in T-lymphocytes.
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Report
(4 results)
Research Products
(80 results)
