| 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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| 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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