Qin H, Rosenbaum J L, Barr M M
Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06520, USA.
Curr Biol. 2001 Mar 20;11(6):457-61. doi: 10.1016/s0960-9822(01)00122-1.
In this report, we show that the Caenorhabditis elegans gene osm-5 is homologous to the Chlamydomonas gene IFT88 and the mouse autosomal recessive polycystic kidney disease (ARPKD) gene, Tg737. The function of this ARPKD gene may be evolutionarily conserved: mutations result in defective ciliogenesis in worms [1], algae [2], and mice [2, 3]. Intraflagellar transport (IFT) is essential for the development and maintenance of motile and sensory cilia [4]. The biochemically isolated IFT particle from Chlamydomonas flagella is composed of 16 polypeptides in one of two Complexes (A and B) [5, 6] whose movement is powered by kinesin II (anterograde) and cytoplasmic dynein (retrograde) [7-9]. We demonstrate that OSM-5 (a Complex B polypeptide), DAF-10 and CHE-11 (two Complex A polypeptides), and CHE-2 [10], a previously uncategorized IFT polypeptide, all move at the same rate in C. elegans sensory cilia. In the absence of osm-5, the C. elegans autosomal dominant PKD (ADPKD) gene products [11] accumulate in stunted cilia, suggesting that abnormal or lack of cilia or defects in IFT may result in diseases such as polycystic kidney disease (PKD).
在本报告中,我们表明秀丽隐杆线虫基因osm-5与衣藻基因IFT88以及小鼠常染色体隐性多囊肾病(ARPKD)基因Tg737同源。该ARPKD基因的功能可能在进化上是保守的:其突变会导致线虫[1]、藻类[2]和小鼠[2,3]中纤毛发生缺陷。鞭毛内运输(IFT)对于运动性和感觉性纤毛的发育和维持至关重要[4]。从衣藻鞭毛中通过生化方法分离出的IFT颗粒由两个复合体(A和B)之一中的16种多肽组成[5,6],其运动由驱动蛋白II(顺行)和胞质动力蛋白(逆行)提供动力[7-9]。我们证明OSM-5(复合体B多肽)、DAF-10和CHE-11(两个复合体A多肽)以及CHE-2[10](一种先前未分类的IFT多肽)在秀丽隐杆线虫感觉纤毛中均以相同速率移动。在缺乏osm-5的情况下,秀丽隐杆线虫常染色体显性多囊肾病(ADPKD)基因产物[11]在发育不良的纤毛中积累,这表明异常或缺乏纤毛或IFT缺陷可能导致诸如多囊肾病(PKD)等疾病。