PKHD1基因的分子特征和生物功能研究进展  

Molecular Characteristics and Functions of PKHD1

作　　者：付玉龙[1] 吴冠青[1] 

机构地区：[1]中国医学科学院肿瘤医院,北京100021

出　　处：《生物化学与生物物理进展》2009年第6期684-688,共5页Progress In Biochemistry and Biophysics

基　　金：长江学者特聘教授计划;国家自然科学基金(30572205;30672483)资助项目~~

摘　　要：PKHD1(polycystic kidney and hepatic disease1)基因定位于人染色体6p12.2.该基因在基因组内约占500kb,其中大约含86个外显子.目前所知,其最长ORF至少由67个外显子组成,编码一个由4074个氨基酸组成的单次跨膜受体样蛋白,被称为纤囊素(fibrocystin/polycystin,FPC).PKHD1是人类常染色体隐性遗传多囊肾病(autosomal recessive polycystic kidneydisease,ARPKD)的致病基因.在小鼠中,FPC于胚胎期9.5天可在发育中的神经管、气管、原肠管等含管道的器官中被探测到.在人类,FPC在胎肾即开始表达于输尿管芽,并持续表达于输尿管芽分支演变为集合管的整个过程.在成体肾,FPC也主要表达于肾内集合管上皮细胞,其亚细胞定位于上皮细胞的管腔面的顶端,主要分布在细胞纤毛和基体附近.FPC的主要生物功能目前仍未完全明了,新近的研究表明,FPC可能作为一个膜受体样蛋白,将细胞外的信号通过结合与调节TRPP2(PKD2)钙离子介导的通道传递到细胞内,调控体内各管道上皮细胞分化、增殖、极化和移行,从而促成各种生理管道的形成.PKHD1 （polycystic kidney and hepatic disease I）, the causal gene of human autosomal recessive polycystic kidney disease（ARPKD）, is located on chromosome 6p12.2 and covers a genomic region of -500 kb. PKHD1 is among the largest human genes, with a minimum of 86 exons from which multiple transcripts may be generated by alternative splicing. The longest continuous open reading frame consists of 12 222 bp, encoding a 4 074 amino acid protein, designated as fibrocystin/polyductin （FPC）. FPC is predicted to be a receptor like protein, with single transmembrane domain and a short cytoplasmic tail. The expression of mouse FPC can be detected in various duct-containing organs. In mouse embryogenesis, FPC appears in developing neural tube, bronchi, and the primordial gut as early as the day of E9.5. In fetal human kidneys, high level of FPC expression is present in ureteric bud and its expression continues throughout the process of renal tubuobranching. In adult human kidneys, FPC mainly expresses in the epithelia of renal collecting ducts. FPC is subcellularly localized to the primary cilia and concentrated on the basal bodies in renal epithelial cells. The detail function of FPC is still unrevealed, most recent studies demonstrate that FPC, as a receptor, may transduce cell signal by interacting with a trio superfamily TRPP2 （PKD2）, which is a causal gene for ADPKD, and mediate intracellular calcium homeostasis to regulate differentiation, proliferation, migration and polarity of various duct/tubular epithelia, in turn, to modulate the formation of all physiologic ducts, tubules and tracts.

关 键 词：PKHD1 纤囊素 人类遗传性隐性多囊肾疾病 结直肠癌 

分 类 号：Q75[生物学—分子生物学]