Caenorhabditis elegans ciliary protein NPHP-8, the homologue of human RPGRIP1L, is required for ciliogenesis and chemosensation
Caenorhabditis elegans ciliary protein NPHP-8, the homologue of human RPGRIP1L, is required for ciliogenesis and chemosensation
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秀丽隐杆线虫纤毛蛋白 NPHP-8 是人 RPGRIP1L 的同源物，是纤毛发生和化学感应所必需的
DOI：
10.1016/j.bbrc.2011.06.041
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发表时间：
2011-07-08
影响因子：
3.1
通讯作者：
Xu, Tao
中科院分区：
文献类型：
--
作者：
Liu, Lin;Zhang, Mingshu;Xu, Tao
肾痨 (NPHP) 是儿童和年轻人终末期肾衰竭最常见的遗传原因。 NPHP8/RPGRIP1L 是一种新型纤毛基因，当突变时，除了引起 NPHP 之外，还会引起 Joubert 综合征 (JBTS) 和 Meckel 综合征 (MKS)。人们对 NPHP8 的确切功能以及 NPHP8 缺陷如何导致人类疾病知之甚少。在这里，我们研究了秀丽隐杆线虫同源物nphp-8（C09G5.8），并探讨了NPHP-8在纤毛感觉神经元中的可能功能。我们通过 cDNA 末端快速扩增 (RACE) 分析确定了 nphp-8 的基因结构，并发现了以前被忽视的 X-box 基序。此外，NPHP-8 与 NPHP-4 共同定位于纤毛基部的过渡区。 nphp-8 突变导致部分睫状神经元中染料填充异常 (Dyf) 和纤毛长度缩短。此外，nphp-8 突变体对几种挥发性引诱剂的趋化性显着受损。我们的数据表明，NPHP-8/RPGRIP1L 在纤毛形成和纤毛介导的化学感觉中以细胞类型特异性方式发挥重要作用。 (C) 2011 Elsevier Inc. 保留所有权利。
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. (C) 2011 Elsevier Inc. All rights reserved.