Rosenbaum Erica E, Hardie Roger C, Colley Nansi J
Department of Ophthalmology and Visual Sciences, Department of Genetics, University of Wisconsin, Madison, Wisconsin 53792, USA.
Neuron. 2006 Jan 19;49(2):229-41. doi: 10.1016/j.neuron.2005.12.011.
In sensory neurons, successful maturation of signaling molecules and regulation of Ca2+ are essential for cell function and survival. Here, we demonstrate a multifunctional role for calnexin as both a molecular chaperone uniquely required for rhodopsin maturation and a regulator of Ca2+ that enters photoreceptor cells during light stimulation. Mutations in Drosophila calnexin lead to severe defects in rhodopsin (Rh1) expression, whereas other photoreceptor cell proteins are expressed normally. Mutations in calnexin also impair the ability of photoreceptor cells to control cytosolic Ca2+ levels following activation of the light-sensitive TRP channels. Finally, mutations in calnexin lead to retinal degeneration that is enhanced by light, suggesting that calnexin's function as a Ca2+ buffer is important for photoreceptor cell survival. Our results illustrate a critical role for calnexin in Rh1 maturation and Ca2+ regulation and provide genetic evidence that defects in calnexin lead to retinal degeneration.
在感觉神经元中，信号分子的成功成熟和Ca2+的调节对于细胞功能和存活至关重要。在此，我们证明钙连接蛋白具有多功能作用，它既是视紫红质成熟所独特需要的分子伴侣，又是在光刺激期间进入光感受器细胞的Ca2+调节剂。果蝇钙连接蛋白的突变导致视紫红质（Rh1）表达严重缺陷，而其他光感受器细胞蛋白则正常表达。钙连接蛋白的突变还损害了光感受器细胞在激活光敏TRP通道后控制胞质Ca2+水平的能力。最后, 钙连接蛋白的突变导致视网膜变性，且光照会加剧这种变性，这表明钙连接蛋白作为Ca2+缓冲剂的功能对光感受器细胞的存活很重要。我们的结果说明了钙连接蛋白在Rh1成熟和Ca2+调节中的关键作用，并提供了基因证据，证明钙连接蛋白缺陷会导致视网膜变性。
