PKHD1 protein encoded by the gene for autosomal recessive polycystic kidney disease associates with basal bodies and primary cilia in renal epithelial cells
PKHD1 protein encoded by the gene for autosomal recessive polycystic kidney disease associates with basal bodies and primary cilia in renal epithelial cells
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DOI：
10.1073/pnas.0400073101
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发表时间：
2004-02-24
影响因子：
11.1
通讯作者：
Wu, GQ
中科院分区：
文献类型：
--
作者：
Zhang, MZ;Mai, WY;Wu, GQ
多囊肾和肝病1（PKHD 1）基因的突变已被证明是导致。常染色体隐性遗传性多囊肾病（ARPKD），但基因产物（PKHD 1）的细胞功能仍不明确。为了阐明其性质，PKHD 1的空间和时间的表达模式，确定在小鼠，大鼠和人体组织中，通过使用多克隆抗体和单克隆抗体识别的基因产物的各种特定区域。在胚胎发育过程中，PKHD 1广泛表达于上皮衍生物，包括神经小管、肠、肺支气管和肝细胞。在pck大鼠（其大鼠模型与人ARPKD遗传同源）的肾脏中，PKHD 1水平显著降低，但并非完全缺失。在培养的肾细胞中，PKHD 1基因产物与多囊蛋白-2（常染色体显性遗传性多囊病2型的基因产物）共定位于初级纤毛的基体。免疫反应性PKHD 1主要定位于极化上皮细胞的顶端区域，表明其可能参与小管形成和/或管腔结构的维持。PKHD 1在大鼠肾脏中的水平降低及其与多囊蛋白的共定位可能是多囊肾疾病囊肿形成的致病基础。
Mutations of the polycystic kidney and hepatic disease 1 (PKHD1) gene have been shown to cause. autosomal recessive polycystic kidney disease (ARPKD), but the cellular functions of the gene product (PKHD1) remain uncharacterized. To illuminate its properties, the spatial and temporal expression patterns of PKHD1 were determined in mouse, rat, and human tissues by using polyclonal Abs and mAbs recognizing various specific regions of the gene product. During embryogenesis, PKHD1 is widely expressed in epithelial derivatives, including neural tubules, gut, pulmonary bronchi, and hepatic cells. In the kidneys of the pck rats, the rat model of which is genetically homologous to human ARPKD, the level of PKHD1 was significantly, reduced but not completely absent. In cultured renal cells, the PKHD1 gene product colocalized with polycystin-2, the gene product of autosomal dominant polycystic disease type 2, at the basal bodies of primary cilia. Immunoreactive PKHD1 localized predominantly at the apical domain of polarized epithelial cells, suggesting it may be involved in the tubulogenesis and/or maintenance of duct-lumen architecture. Reduced PKHD1 levels in pck rat kidneys and its colocalization with polycystins may underlie the pathogenic basis for cystogenesis in polycystic kidney diseases.