Eley Lorraine, Moochhala Shabbir H, Simms Roslyn, Hildebrandt Friedhelm, Sayer John A
Institute of Human Genetics, International Centre For Life, University of Newcastle upon Tyne, NE1 3BZ, UK.
Biochem Biophys Res Commun. 2008 Jul 11;371(4):877-82. doi: 10.1016/j.bbrc.2008.05.016. Epub 2008 May 12.
Nephronophthisis is characterised by renal fibrosis, tubular basement membrane disruption and corticomedullary cyst formation leading to end stage renal failure. Mutations in NPHP1 account for the underlying genetic defect in 25% of patients with nephronophthisis. Loss of urine concentration ability may be an early feature of nephronophthisis. Using yeast-2-library screening with the SH3 domain of nephrocystin-1 as bait, we identify Ack1 as a novel interaction partner. This interaction is confirmed using exogenous over-expression followed by co-immunoprecipitation. Ack1 is an activated Cdc42-associated kinase, and like nephrocystin-1, is a known interactor of p130Cas. Nephrocystin-1 partially colocalises with Ack1 at cell-cell contacts in IMCD3 cells. In human kidney, nephrocystin-1 expression is limited to cell-cell junctions in renal collecting duct cells. These data define Ack1 as a novel interaction partner of nephrocystin-1 and implicate cell-cell junctions and the renal collecting duct in the pathology of nephronophthisis.
肾单位肾痨的特征是肾纤维化、肾小管基底膜破坏和皮质髓质囊肿形成，最终导致终末期肾衰竭。NPHP1基因突变占肾单位肾痨患者潜在遗传缺陷的25%。尿液浓缩能力丧失可能是肾单位肾痨的早期特征。我们以肾囊肿蛋白-1的SH3结构域为诱饵进行酵母双杂交文库筛选，鉴定出Ack1是一种新的相互作用蛋白。通过外源过表达随后进行免疫共沉淀证实了这种相互作用。Ack1是一种活化的Cdc42相关激酶，与肾囊肿蛋白-1一样，是已知的p130Cas相互作用蛋白。在IMCD3细胞中，肾囊肿蛋白-1与Ack1在细胞间接触部位部分共定位。在人肾脏中，肾囊肿蛋白-1的表达仅限于肾集合管细胞的细胞间连接。这些数据将Ack1定义为肾囊肿蛋白-1的一种新的相互作用蛋白，并提示细胞间连接和肾集合管与肾单位肾痨的病理过程有关。
