Tissue and cellular localization of a novel polycystic kidney disease-like gene product, polycystin-L
Tissue and cellular localization of a novel polycystic kidney disease-like gene product, polycystin-L
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DOI：
10.1681/asn.v132293
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发表时间：
2002-02-01
影响因子：
13.6
通讯作者：
Zhou, J
中科院分区：
文献类型：
--
作者：
Basora, N;Nomura, H;Zhou, J
多囊蛋白-L(Polycystin-L，PCL)是多囊蛋白家族的第三个成员，在非洲爪哇卵母细胞中表达时，可作为钙离子调控的非选择性阳离子通道。多囊蛋白-1和-2在常染色体显性遗传性多囊肾病(ADPKD)中发生突变，但PCL在疾病中的作用尚未确定。本研究制备了抗人PCL羧基末端结构域的抗肽多克隆抗血清，并用间接免疫荧光法测定了PCL在发育小鼠和成年小鼠体内的表达和分布。结果表明，PCL主要在成年小鼠组织中表达，并且比多囊蛋白-1或-2有更多的限制性表达模式。在肾脏中，PCL在胚胎16岁时首次检测到表达，并在成年后水平增加。PCL主要定位于内髓集合管主细胞的顶端。PCL也在视网膜、睾丸、肝脏、胰腺、心脏和脾的不同类型的细胞中发现，但在肺中没有检测到。这些数据与PCL通道活性的证据相结合，对于阐明这一新的阳离子通道的生理作用至关重要，并可能有助于阐明内髓集合管和多囊蛋白的功能。PCL的表达模式表明它不太可能是ADPKD的候选基因，但它仍然是其他尚未定位的人类囊性疾病的潜在候选基因。
Polycystin-L (PCL), the third member of the polycystin family of proteins, functions as a Ca2+-modulated nonselective cation channel when expressed in Xenopus oocytes. Polycystin-1 and -2 are mutated in autosomal-dominant polycystic kidney disease (ADPKD), but the role of PCL in disease has not been determined. In this study, an anti-peptide polyclonal antiserum was generated against the carboxyl terminal domain of human PCL and used to determine the patterns of expression and distribution of PCL by indirect immunofluorescence in both developing and adult mice. The results show that PCL is predominantly expressed in adult mouse tissues and has a more restricted pattern of expression than either polycystin-1 or -2. In the kidney, PCL expression was first detected at E16, and levels increased into adulthood. Localization of PCL was predominantly found in the apical region of the principal cells of inner medullary collecting ducts. PCL was also found in discrete cell types of the retina, testis, liver, pancreas, heart, and spleen, but it was not detected in the lung. These data in combination with evidence of PCL channel activity are crucial for elucidating the physiologic role of this novel cation channel and may shed light on the function of inner medullary collecting ducts and polycystins. The expression pattern of PCL suggests that it is unlikely to be a candidate gene for ADPKD, but it remains a potential candidate for other as yet unmapped human cystic disorders.