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First published online 2 December 2008
doi: 10.1242/jcs.037408

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Localization of Inv in a distinctive intraciliary compartment requires the C-terminal ninein-homolog-containing region

Dai Shiba¹, Yoshihisa Yamaoka^2,*, Haruo Hagiwara^3,*, Tetsuro Takamatsu², Hiroshi Hamada⁴ and Takahiko Yokoyama^1,

¹ Department of Anatomy and Developmental Biology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
² Department of Pathology and Cell Regulation, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
³ Department of Anatomy and Cell Biology, Gunma University Graduate School of Medicine, Gunma, Japan
⁴ Developmental Genetics Group, Graduate School of Frontier Biosciences, Osaka University, Osaka, Japan

Author for correspondence (e-mail: tyoko{at}koto.kpu-m.ac.jp)

Accepted 17 September 2008

The primary cilium is an antenna-like structure extending from the surface of most vertebrate cells. Loss or mutation of ciliary proteins can lead to polycystic kidney disease and other developmental abnormalities. inv mutant mice develop multiple renal cysts and are a model for human nephronophthisis type 2. The mouse Inv gene encodes a 1062-amino-acid protein that is localized in primary cilia. In this study, we show that the Inv protein (also known as inversin) is localized at a distinctive proximal segment of the primary cilium, using GFP-tagged Inv constructs and anti-Inv antibody. We named this segment the Inv compartment of the cilium. Further investigation of the Inv protein showed that 60 amino acids at its C-terminal, which contains ninein homologous sequences, are crucial for its localization to the Inv compartment. Fluorescence recovery after photobleaching analysis revealed that the Inv protein was dynamic within this compartment. These results suggest that localization of the Inv protein to the Inv compartment is actively regulated. The present study revealed that the primary cilium has a distinct molecular compartment in the body of the primary cilium with a specific confining and trafficking machinery that has not been detected previously by morphological examination.

Key words: Primary cilia, Inv, Cilia localization signal, Inversin

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