Brereton H M, Harland M L, Auld A M, Barritt G J
Department of Medical Biochemistry, School of Medicine, Flinders University, Adelaide, South Australia.
Mol Cell Biochem. 2000 Nov;214(1-2):63-74. doi: 10.1023/a:1007193720930.
The role of the TRP-1 protein, an animal cell homologue of the Drosophila transient receptor potential Ca2+ channel, in store-operated Ca2+ inflow in Xenopus laevis oocytes was investigated. A strategy involving RT-PCR and 3' and 5' rapid amplification of cDNA ends (RACE) was used to confirm and extend previous knowledge of the nucleotide and predicted amino acid sequences of Xenopus TRP-1 (xTRP-1). The predicted amino acid sequence was used to prepare an anti-TRP-l polyclonal antibody which detected the endogenous oocyte xTRP-1 protein and the human TRPC-1 protein expressed in Xenopus oocytes. Ca2+ inflow (measured using fura-2) initiated by 3-deoxy-3-fluoroinositol 1,4,5-trisphosphate (InsP3F) or lysophosphatidic acid (LPA) was completely inhibited by low concentrations of lanthanides (IC50 = 0.5 microM), indicating that InsP3F and LPA principally activate store-operated Ca2+ channels (SOCs). Antisense cRNA or antisense oligodeoxynucleotides, based on different regions of the xTRP-1 cDNA sequence, when injected into Xenopus oocytes, did not inhibit InsP3F-, LPA- or thapsigargin-stimulated Ca2+ inflow. Oocytes expressing the hTRPC-1 protein, which is 96% similar to xTRP-1, exhibited no detectable enhancement of either basal or InsP3F-stimulated Ca2+ inflow and only a very small enhancement of LPA-stimulated Ca2+ in-flow compared with control oocytes. It is concluded that the endogenous xTRP-1 protein is unlikely to be responsible for Ca2+ inflow through the previously-characterised Ca2+ -specific SOCs which are found in Xenopus oocytes. It is considered that xTRP-1 is likely to be a receptor-activated non-selective cation channel such as the channel activated by maitotoxin.
研究了果蝇瞬时受体电位Ca2+通道的动物细胞同源物TRP-1蛋白在非洲爪蟾卵母细胞储存操纵性Ca2+内流中的作用。采用逆转录聚合酶链反应(RT-PCR)以及cDNA末端的3'和5'快速扩增(RACE)策略,以确认并拓展之前关于非洲爪蟾TRP-1(xTRP-1)核苷酸和预测氨基酸序列的认识。利用预测的氨基酸序列制备了抗TRP-1多克隆抗体,该抗体可检测内源性卵母细胞xTRP-1蛋白以及在非洲爪蟾卵母细胞中表达的人TRPC-1蛋白。由3-脱氧-3-氟肌醇1,4,5-三磷酸(InsP3F)或溶血磷脂酸(LPA)引发的Ca2+内流(使用fura-2测量)被低浓度镧系元素完全抑制(半数抑制浓度IC50 = 0.5 microM),这表明InsP3F和LPA主要激活储存操纵性Ca2+通道(SOCs)。基于xTRP-1 cDNA序列不同区域的反义cRNA或反义寡脱氧核苷酸注入非洲爪蟾卵母细胞后,并未抑制InsP3F、LPA或毒胡萝卜素刺激的Ca2+内流。与对照卵母细胞相比,表达与xTRP-1有96%相似性的hTRPC-1蛋白的卵母细胞,其基础Ca2+内流或InsP3F刺激的Ca2+内流均未检测到增强,LPA刺激的Ca2+内流仅略有增强。结论是,内源性xTRP-1蛋白不太可能是非洲爪蟾卵母细胞中先前鉴定的Ca2+特异性SOCs介导Ca2+内流的原因。据认为,xTRP-1可能是一种受体激活的非选择性阳离子通道,如被刺尾鱼毒素激活的通道。