Department of Anatomy and Developmental Biology, Kyoto Prefectural University of Medicine, Japan.
Cytoskeleton (Hoboken). 2010 Feb;67(2):112-9. doi: 10.1002/cm.20428.
A primary cilium is an antenna-like structure extending from the surface of most vertebrate cells. It is structurally divided along its vertical axis into sub-compartments that include the ciliary tip, the shaft, the ciliary necklace segment, the transitional zone and the basal body. We recently discovered that the shaft of the primary cilia has a distinct molecular compartment, termed the "Inv compartment", which is characterized by the accumulation of Inv at the base of primary cilia. Inv was discovered as a causative gene in inv mutant mice. It was later found to be responsible for the infantile type of nephronophthisis (NPHP2). Nephronophthisis (NPHP) is an autosomal recessive kidney disease. Nine causative genes have been identified, with all examined products thought to function in cilia, basal body and/or centrioles. However, their exact intra-ciliary localization and relationship have not been clear. Here, we report that products of Nphp3 and Nek8 (the mouse orthologs of the causative genes for NPHP3 and NPHP9, respectively) localize to the Inv compartment. We also show that Inv is essential for the compartmental localization of Nphp3 and Nek8, whereas localization of Inv does not require Nphp3 or Nek8. Nphp1 and Nphp4 also localize at the proximal region of the cilium, but not in Inv compartment. Our results indicate that Inv acts as an anchor for Nphp3 and Nek8 in the Inv compartment, and suggest that Inv compartment is a candidate site for intra-ciliary interaction of Inv, Nphp3 and Nek8.
一个初级纤毛是一个从大多数脊椎动物细胞表面伸出的天线状结构。它在垂直轴线上沿其结构分为几个亚区，包括纤毛尖端、轴、纤毛项链段、过渡区和基体。我们最近发现，初级纤毛的轴具有独特的分子区室，称为“Inv 区室”，其特征是 Inv 在初级纤毛的基部积累。Inv 作为 inv 突变小鼠的致病基因被发现。后来发现它负责婴儿型肾单位肾痨（NPHP2）。肾单位肾痨（NPHP）是一种常染色体隐性肾脏疾病。已经确定了九个致病基因，所有检查的产物都被认为在纤毛、基体和/或中心粒中发挥作用。然而，它们的确切细胞内定位和关系尚不清楚。在这里，我们报告 Nphp3 和 Nek8 的产物（分别为 NPHP3 和 NPHP9 的致病基因的小鼠同源物）定位于 Inv 区室。我们还表明，Inv 对于 Nphp3 和 Nek8 的区室定位是必不可少的，而 Inv 的定位不需要 Nphp3 或 Nek8。Nphp1 和 Nphp4 也定位于纤毛的近端区域，但不在 Inv 区室中。我们的结果表明，Inv 作为 Inv 区室中 Nphp3 和 Nek8 的锚定物，并且表明 Inv 区室是 Inv、Nphp3 和 Nek8 细胞内相互作用的候选部位。
