PDF(Pubmed)
Abstract：
Visual signal transduction takes place within a stack of flattened membranous \'discs\' enclosed within the light-sensitive photoreceptor outer segment. The highly curved rims of these discs, formed in the process of disc enclosure, are fortified by large hetero-oligomeric complexes of two homologous tetraspanin proteins, PRPH2 (a.k.a. peripherin-2 or rds) and ROM1. While mutations in PRPH2 affect the formation of disc rims, the role of ROM1 remains poorly understood. In this study, we found that the knockout of ROM1 causes a compensatory increase in the disc content of PRPH2. Despite this increase, discs of ROM1 knockout mice displayed a delay in disc enclosure associated with a large diameter and lack of incisures in mature discs. Strikingly, further increasing the level of PRPH2 rescued these morphological defects. We next showed that disc rims are still formed in a knockin mouse in which the tetraspanin body of PRPH2 was replaced with that of ROM1. Together, these results demonstrate that, despite its contribution to the formation of disc rims, ROM1 can be replaced by an excess of PRPH2 for timely enclosure of newly forming discs and establishing normal outer segment structure.
摘要：
视觉信号转导发生在光敏感光体外段内的一堆扁平膜“盘”内。这些圆盘的高度弯曲的边缘，在光盘外壳的过程中形成的，由两种同源四跨膜蛋白的大型异源寡聚复合物强化，PRPH2（又名外周蛋白2或rds）和ROM1。虽然PRPH2中的突变会影响椎间盘边缘的形成，ROM1的作用仍然知之甚少。在这项研究中,我们发现，敲除ROM1会导致PRPH2的椎间盘含量补偿性增加。尽管增加了,ROM1敲除小鼠的椎间盘显示出与大直径和成熟椎间盘缺乏相关的椎间盘封闭延迟。引人注目的是，进一步增加PRPH2的水平挽救了这些形态缺陷。接下来，我们表明，在敲入小鼠中仍形成圆盘边缘，其中PRPH2的四跨膜蛋白体被ROM1的体代替。一起,这些结果表明，尽管它对圆盘边缘的形成有贡献，ROM1可以用过量的PRPH2代替，以便及时封闭新形成的圆盘并建立正常的外段结构。
