Dissecting independent channel and scaffolding roles of the Drosophila transient receptor potential channel.
Dissecting independent channel and scaffolding roles of the Drosophila transient receptor potential channel.
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DOI：
10.1083/jcb.200508030
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发表时间：
2005-11-21
影响因子：
7.8
通讯作者：
Montell, Craig
中科院分区：
文献类型：
--
作者：
Wang, Tao;Jiao, Yuchen;Montell, Craig
果蝇瞬时受体电位（TRP）具有双重作用，既作为阳离子通道，又作为PDZ蛋白INAD（失活无后电位D）的分子锚。trp的突变导致视觉传导受损、INAD的错误定位和视网膜变性。然而，特异性改变TRP通道功能的影响尚不清楚，因为现有的功能丧失等位基因大大降低了蛋白质表达。在目前的研究中，我们描述了一组新的色氨酸等位基因的分离，包括色氨酸14与氨基酸取代并列的TRP结构域。Trp 14果蝇稳定表达TRP，并显示正常的分子锚定，但通道功能有缺陷。单独消除trp Δ 1272中的锚定功能对视网膜形态学的影响很小，而通道功能的破坏引起了严重的光诱导细胞死亡。这种视网膜变性被Na+/Ca 2+交换剂CalX的消除大大抑制，表明细胞死亡主要是由于缺乏Ca 2+进入而不是TRP锚定功能的破坏。
Drosophila transient receptor potential (TRP) serves dual roles as a cation channel and as a molecular anchor for the PDZ protein, INAD (inactivation no afterpotential D). Null mutations in trp cause impairment of visual transduction, mislocalization of INAD, and retinal degeneration. However, the impact of specifically altering TRP channel function is not known because existing loss-of-function alleles greatly reduce protein expression. In the current study we describe the isolation of a set of new trp alleles, including trp 14 with an amino acid substitution juxtaposed to the TRP domain. The trp 14 flies stably express TRP and display normal molecular anchoring, but defective channel function. Elimination of the anchoring function alone in trp Δ 1272, had minor effects on retinal morphology whereas disruption of channel function caused profound light-induced cell death. This retinal degeneration was greatly suppressed by elimination of the Na+/Ca2+ exchanger, CalX, indicating that the cell death was due primarily to deficient Ca2+ entry rather than disruption of the TRP-anchoring function.