Alloway P G, Howard L, Dolph P J
Department of Biological Sciences, Dartmouth College, Hanover, New Hampshire 03755, USA.
Neuron. 2000 Oct;28(1):129-38. doi: 10.1016/s0896-6273(00)00091-x.
Although many different mutations in humans and Drosophila cause retinal degeneration, in most cases, a molecular mechanism for the degeneration has not been found. We now demonstrate the existence of stable, persistent complexes between rhodopsin and its regulatory protein arrestin in several different retinal degeneration mutants. Elimination of these rhodopsin-arrestin complexes by removing either rhodopsin or arrestin rescues the degeneration phenotype. Furthermore, we show that the accumulation of these complexes triggers apoptotic cell death and that the observed retinal degeneration requires the endocytic machinery. This suggests that the endocytosis of rhodopsin-arrestin complexes is a molecular mechanism for the initiation of retinal degeneration. We propose that an identical mechanism may be responsible for the pathology found in a subset of human retinal degenerative disorders.
尽管人类和果蝇中许多不同的突变会导致视网膜变性，但在大多数情况下，尚未发现变性的分子机制。我们现在证明，在几种不同的视网膜变性突变体中，视紫红质与其调节蛋白抑制蛋白之间存在稳定、持久的复合物。通过去除视紫红质或抑制蛋白来消除这些视紫红质 - 抑制蛋白复合物，可挽救变性表型。此外，我们表明这些复合物的积累会触发凋亡性细胞死亡，并且观察到的视网膜变性需要内吞机制。这表明视紫红质 - 抑制蛋白复合物的内吞作用是视网膜变性起始的分子机制。我们提出，相同的机制可能是导致一部分人类视网膜退行性疾病病理变化的原因。
