DeLisle S, Blondel O, Longo F J, Schnabel W E, Bell G I, Welsh M J
Veterans Affairs Medical Center, Iowa City, Iowa, USA.
Am J Physiol. 1996 Apr;270(4 Pt 1):C1255-61. doi: 10.1152/ajpcell.1996.270.4.C1255.
The receptors for the second messenger inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] form a family of closely related proteins that play an important role in regulating the free intracellular Ca2+ concentration. To test the hypothesis that changing the expression level of Ins(1,4,5)P3 receptors could alter the Ins(1,4,5)P3-mediated Ca2+ signal, we overexpressed Ins(1,4,5)P3 receptor type 1 (InsP3R-1) or type 3 (InsP3R-3) in Xenopus laevis oocytes. Expression of InsP3R-1 increased the velocity of the propagating waves of intracellular Ca2+ release but did not affect the Ins(1,4,5)P3-induced entry of extracellular Ca2+ across the plasma membrane. In contrast, expression of intracellular Ca2+ but markedly increased the magnitude and duration of Ca2+ influx. Immunolocalization studied revealed InsP3R-3 at the endoplasmic reticulum, with a relatively stronger signal at or near the plasma membrane. The results suggest that changing the expression level of an InsP3R can alter the Ins(1,4,5)P3-mediated Ca2+ signal and that InsP3R-1 and InsP3R-3 may have different biological functions.
第二信使肌醇1,4,5 -三磷酸[Ins(1,4,5)P3]的受体构成了一个密切相关的蛋白质家族,它们在调节细胞内游离Ca2+浓度方面发挥着重要作用。为了验证改变Ins(1,4,5)P3受体的表达水平是否会改变Ins(1,4,5)P3介导的Ca2+信号这一假设,我们在非洲爪蟾卵母细胞中过表达了1型Ins(1,4,5)P3受体(InsP3R - 1)或3型Ins(1,4,5)P3受体(InsP3R - 3)。InsP3R - 1的表达增加了细胞内Ca2+释放传播波的速度,但不影响Ins(1,4,5)P3诱导的细胞外Ca2+跨质膜的内流。相比之下,InsP3R - 3的表达对细胞内Ca2+的释放影响不大,但显著增加了Ca2+内流的幅度和持续时间。免疫定位研究显示InsP3R - 3在内质网上,在质膜处或其附近有相对较强的信号。结果表明,改变InsP3R的表达水平可以改变Ins(1,4,5)P3介导的Ca2+信号,并且InsP3R - 1和InsP3R - 3可能具有不同的生物学功能。