A C-terminal PDZ binding domain modulates the function and localization of Kv1.3 channels.
A C-terminal PDZ binding domain modulates the function and localization of Kv1.3 channels.
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DOI：
10.1016/j.yexcr.2011.06.009
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发表时间：
2011-10-01
影响因子：
3.7
通讯作者：
Morielli, Anthony D.
中科院分区：
文献类型：
--
作者：
Doczi, Megan A.;Damon, Deborah H.;Morielli, Anthony D.
电压门控钾通道Kv1.3在调节从T淋巴细胞到神经元的多种细胞类型的膜兴奋性中起重要作用。在本研究中，我们测试的假设，C-末端PDZ结合域调制的功能和本地化的Kv1.3。我们创建了Kv1.3的突变形式，其缺少C末端PDZ结合结构域的最后三个氨基酸（Kv1.3ΔTDV）。这种形式的Kv1.3不结合含PDZ结构域的蛋白质PSD 95。我们将野生型和突变型Kv1.3转染到HEK 293细胞中，并确定突变是否影响电流、高尔基体定位和通道的表面表达。我们发现转染Kv1.3ΔTDV的细胞比转染Kv1.3的细胞具有更大的电流和更低的高尔基体定位。截断的C-末端PDZ结构域不影响Kv1.3的表面表达。这些发现表明，PDZ依赖的相互作用影响Kv1.3的定位和功能。电流和高尔基体定位改变而表面表达没有相应变化的发现表明PDZ相互作用通过独立机制影响定位和功能。
The voltage-gated potassium channel, Kv1.3, plays an important role in regulating membrane excitability in diverse cell types ranging from T-lymphocytes to neurons. In the present study, we test the hypothesis that the C-terminal PDZ binding domain modulates the function and localization of Kv1.3. We created a mutant form of Kv1.3 that lacked the last three amino acids of the C-terminal PDZ-binding domain (Kv1.3ΔTDV). This form of Kv1.3 did not bind the PDZ domain containing protein, PSD95. We transfected wild type and mutant Kv1.3 into HEK293 cells and determined if the mutation affected current, Golgi localization, and surface expression of the channel. We found that cells transfected with Kv1.3ΔTDV had greater current and lower Golgi localization than those transfected with Kv1.3. Truncation of the C-terminal PDZ domain did not affect surface expression of Kv1.3. These findings suggest that PDZ-dependent interactions affect both Kv1.3 localization and function. The finding that current and Golgi localization changed without a corresponding change in surface expression suggests that PDZ interactions affect localization and function via independent mechanisms.
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