Chakraborty Sumita, Hasan Gaiti
National Centre for Biological Sciences, Tata Institute of Fundamental ResearchBangalore, India.
Front Mol Neurosci. 2017 Apr 20;10:111. doi: 10.3389/fnmol.2017.00111. eCollection 2017.
Inositol 1,4,5-trisphosphate receptors (IPR) are Ca channels on the neuronal endoplasmic reticulum (ER) membrane. They are gated by IP, produced upon external stimulation and activation of G protein-coupled receptors on the plasma membrane (PM). IP-mediated Ca release, and the resulting depletion of the ER store, triggers entry of extracellular Ca by store-operated Ca entry (SOCE). Mutations in IPR attenuate SOCE. Compromised IPR function and SOCE during pupal development of leads to flight deficits and mimics suppression of neuronal activity during pupal or adult development. To understand the effect of compromised IPR function on pupal neuronal calcium signaling, we examined the effects of mutations in the IPR gene () on Ca signals in cultured neurons derived from pupae. We observed increased spontaneous Ca influx across the PM of isolated pupal neurons with mutant IPR and also a loss of SOCE. Both spontaneous Ca influx and reduced SOCE were reversed by over-expression of and , which encode the SOCE Ca channel and the ER Ca-sensor that regulates it, respectively. Expression of voltage-gated Ca channels ( and ) was significantly reduced in mutant neurons. However, expression of mRNAs and transient receptor potential (TRP) protein were increased, suggesting that TRP channels might contribute to the increased spontaneous Ca influx in neurons with mutant IPR. Thus, IPR/SOCE modulates spontaneous Ca influx and expression of PM Ca channels in pupal neurons. Spontaneous Ca influx compensates for the loss of SOCE in mutant neurons.
肌醇1,4,5 -三磷酸受体（IPR）是神经元内质网（ER）膜上的钙通道。它们由质膜（PM）上G蛋白偶联受体受到外部刺激并激活后产生的IP3门控。IP3介导的钙释放以及内质网钙库的耗尽，通过钙库操纵的钙内流（SOCE）触发细胞外钙的进入。IPR中的突变会减弱SOCE。在蛹发育过程中IPR功能受损和SOCE受损会导致飞行缺陷，并模拟蛹期或成虫发育过程中神经元活动的抑制。为了了解IPR功能受损对蛹期神经元钙信号的影响，我们研究了IPR基因（）中的突变对源自蛹的培养神经元中钙信号的影响。我们观察到，具有突变IPR的分离蛹神经元跨质膜的自发钙内流增加，同时SOCE丧失。分别编码SOCE钙通道及其调节的内质网钙传感器的和的过表达可逆转自发钙内流和SOCE降低。在突变神经元中，电压门控钙通道（和）的表达显著降低。然而，mRNA和瞬时受体电位（TRP）蛋白的表达增加，这表明TRP通道可能导致具有突变IPR的神经元中自发钙内流增加。因此，IPR/SOCE调节蛹期神经元中的自发钙内流和质膜钙通道的表达。自发钙内流补偿了突变神经元中SOCE的丧失。
