光感受器连接纤毛(CC)在结构上类似于初级纤毛的过渡区(TZ),并控制内外节(OS)之间的分子运输。具有潜在CC缺陷的视网膜营养不良表现为广泛的综合征,称为纤毛病以及非综合征性视网膜变性。尽管进行了广泛的研究,在整个感光CC中蛋白质运输的机制中仍然存在许多问题。这里,我们基因灭活了小鼠Tmem138,该基因编码定位于睫状TZ并与纤毛病相关的推定跨膜蛋白。Tmem138的种系缺失废除了OS形态发生,其次是快速的光感受器变性。发现Tmem138位于光感受器CC,并且需要将Ahi1定位到CC的远端子域。在检查的OS蛋白质组中,在OS形态发生之前,视紫红质在整个突变细胞体中被错误定位。成熟棒中Tmem138的消融概括了种系突变体的分子变化,导致光盘更新失败和操作系统解体。此外,Tmem138与视紫红质和相关蛋白Tmem231相互作用,后者的纤毛定位在突变的光感受器中也发生了改变。一起来看,这些结果表明Tmem138在CC的功能组织中的关键作用,这对于视紫红质定位和OS生物发生至关重要。
Photoreceptor connecting cilium (CC) is structurally analogous to the transition zone (TZ) of primary cilia and gates the molecular trafficking between the inner and the outer segment (OS). Retinal dystrophies with underlying CC defects are manifested in a broad array of syndromic conditions known as ciliopathies as well as nonsyndromic retinal degenerations. Despite extensive studies, many questions remain in the mechanism of protein trafficking across the photoreceptor CC. Here, we genetically inactivated mouse Tmem138, a gene encoding a putative transmembrane protein localized to the ciliary TZ and linked to ciliopathies. Germline deletion of Tmem138 abolished OS morphogenesis, followed by rapid photoreceptor degeneration. Tmem138 was found localized to the photoreceptor CC and was required for localization of Ahi1 to the distal subdomain of the CC. Among the examined set of OS proteins, rhodopsin was mislocalized throughout the mutant cell body prior to OS morphogenesis. Ablation of Tmem138 in mature rods recapitulated the molecular changes in the germline mutants, causing failure of disc renewal and disintegration of the OS. Furthermore, Tmem138 interacts reciprocally with rhodopsin and a related protein Tmem231, and the ciliary localization of the latter was also altered in the mutant photoreceptors. Taken together, these results suggest a crucial role of Tmem138 in the functional organization of the CC, which is essential for rhodopsin localization and OS biogenesis.