Joint Laboratory of the Institute of Biophysics & Huazhong University of Science and Technology, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, PR China.
Biochem Biophys Res Commun. 2011 Jul 8;410(3):626-31. doi: 10.1016/j.bbrc.2011.06.041. Epub 2011 Jun 13.
Nephronophthisis (NPHP) is the most frequent genetic cause of end-stage renal failure in children and young adults. NPHP8/RPGRIP1L is a novel ciliary gene that, when mutated, in addition to causing NPHP, also causes Joubert syndrome (JBTS) and Meckel syndrome (MKS). The exact function of NPHP8 and how defects in NPHP8 lead to human diseases are poorly understood. Here, we studied the Caenorhabditis elegans homolog nphp-8 (C09G5.8) and explored the possible function of NPHP-8 in ciliated sensory neurons. We determined the gene structure of nphp-8 through rapid amplification of cDNA ends (RACE) analysis and discovered an X-box motif that had been previously overlooked. Moreover, NPHP-8 co-localized with NPHP-4 at the transition zone at the base of cilia. Mutation of nphp-8 led to abnormal dye filling (Dyf) and shorter cilia lengths in a subset of ciliary neurons. In addition, chemotaxis to several volatile attractants was significantly impaired in nphp-8 mutants. Our data suggest that NPHP-8/RPGRIP1L plays an important role in cilia formation and cilia-mediated chemosensation in a cell type-specific manner.
常染色体隐性遗传的多囊肾病（NPHP）是儿童和青年终末期肾衰竭的最常见遗传原因。NPHP8/RPGRIP1L 是一种新型纤毛基因，当其突变时，除了引起 NPHP 外，还引起 Joubert 综合征（JBTS）和 Meckel 综合征（MKS）。NPHP8 的确切功能以及 NPHP8 缺陷如何导致人类疾病还知之甚少。在这里，我们研究了秀丽隐杆线虫同源物 nphp-8（C09G5.8），并探索了 NPHP-8 在纤毛感觉神经元中的可能功能。我们通过快速扩增 cDNA 末端（RACE）分析确定了 nphp-8 的基因结构，并发现了以前被忽视的 X 框基序。此外，NPHP-8 与 NPHP-4 一起在纤毛基部的过渡区共定位。nphp-8 的突变导致一部分纤毛神经元的异常染料填充（Dyf）和纤毛长度变短。此外，nphp-8 突变体对几种挥发性引诱剂的趋化性显著受损。我们的数据表明，NPHP-8/RPGRIP1L 以细胞类型特异性的方式在纤毛形成和纤毛介导的化学感觉中发挥重要作用。
