Goldberg Andrew F X
Eye Research Institute, Oakland University, Rochester, Michigan 48309, USA.
Int Rev Cytol. 2006;253:131-75. doi: 10.1016/S0074-7696(06)53004-9.
The vertebrate photoreceptor outer segment (OS) is a highly structured and dynamic organelle specialized to transduce light signals. The elaborate membranous architecture of the OS requires peripherin/rds (P/rds), an integral membrane protein and tetraspanin protein family member. Gene-level defects in P/rds cause a broad variety of late-onset progressive retinal degenerations in humans and dysmorphic photoreceptors in murine and Xenopus models. Although proposed to fulfill numerous roles related to OS structural stability and renewal, P/rds molecular function remains uncertain. An increasingly resolved model of this protein's oligomeric structure can account for disease inheritance patterns and severity in some instances. Nonetheless, the pathogenic mechanisms underlying the uniquely broad spectrum of retinal diseases associated with P/rds defects are not currently well understood. Recent findings point to the possibility that P/rds acts as a multifunctional scaffolding protein for OS architecture and that partial-loss-of-function mutations contribute to the hallmark phenotypic heterogeneity associated with inherited defects in RDS.
脊椎动物光感受器外段（OS）是一种高度结构化且动态的细胞器，专门用于转导光信号。OS复杂的膜结构需要外周蛋白/视网膜变性慢（P/rds），它是一种整合膜蛋白，也是四跨膜蛋白家族成员。P/rds基因水平的缺陷会导致人类多种迟发性进行性视网膜变性，以及小鼠和非洲爪蟾模型中的光感受器形态异常。尽管有人提出P/rds在OS结构稳定性和更新方面发挥多种作用，但其分子功能仍不确定。该蛋白寡聚体结构的一个日益清晰的模型在某些情况下可以解释疾病的遗传模式和严重程度。然而，目前对于与P/rds缺陷相关的独特广泛视网膜疾病的致病机制尚未完全理解。最近的研究结果表明，P/rds可能作为OS结构的多功能支架蛋白，部分功能丧失突变导致了与RDS遗传缺陷相关的标志性表型异质性。
