Collectrin, a collecting duct-specific transmembrane glycoprotein, is a novel homolog of ACE2 and is developmentally regulated in embryonic kidneys
Collectrin, a collecting duct-specific transmembrane glycoprotein, is a novel homolog of ACE2 and is developmentally regulated in embryonic kidneys
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DOI：
10.1074/jbc.m006723200
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发表时间：
2001-05-18
影响因子：
4.8
通讯作者：
Makino, H
中科院分区：
文献类型：
--
作者：
Zhang, H;Wada, J;Makino, H
Collectrin是血管紧张素转换酶相关羧肽酶（ACE 2）的一种新的同源物，在5/6例肥大期的消融肾中表达上调。Collectrin由222个氨基酸组成，具有一个明显的信号肽和一个跨膜结构域;该序列在小鼠、大鼠和人中是保守的，具有81.9%的同一性。人collectrin与AGES的非催化细胞外、跨膜和胞质结构域具有47.8%的同一性;然而，与ACE和AGES不同，collectrin缺乏活性二肽基羧肽酶催化结构域。collectrin mRNA转录物仅在肾脏中表达。原位杂交显示其mRNA在肾集合管中表达，免疫组织化学显示其定位于集合管的腔表面和细胞质。使用[S-35]甲硫氨酸标记的肾皮质和内髓集合管细胞（即M-1和mIMCD-3）进行的免疫沉淀研究表明，蛋白质大小与32 kDa相似。在小鼠肾脏发育过程中，在妊娠第13天可检测到mRNA信号，并在输尿管芽支中观察到蛋白产物。其表达在妊娠后期逐渐增加，延伸到新生儿期，然后在成年期减少。肾消融后肥大肾脏中collectrin的上调表达和发育过程中受限的时空表达表明在进行性肾衰竭和肾器官发生过程中可能起作用。
Collectrin, a novel homolog of angiotensin-converting enzyme-related carboxypeptidase (ACE2), was identified during polymerase chain reaction-based cDNA subtraction and up-regulated in 5/6 ablated kidneys at hypertrophic phase. Collectrin, with 222 amino acids, has an apparent signal peptide and a transmembrane domain; the sequence is conserved in mouse, rat, and human and shares 81.9% identity. Human collectrin has 47.8% identity with non-catalytic extracellular, transmembrane, and cytosolic domains of AGES; however, unlike ACE and AGES, collectrin lacks active dipeptidyl carboxypeptidase catalytic domains. The collectrin mRNA transcripts are expressed exclusively in the kidney. In situ hybridization reveals its mRNA expression in renal collecting ducts, and immunohistochemistry shows that it is localized to the luminal surface and cytoplasm of collecting ducts. Immunoprecipitation studies, using [S-35]methionine-labeled renal cortical and inner medullar collecting duct cells, i.e. M-1 and mIMCD-3, indicate that the protein size is similar to 32 kDa. During the development of mouse kidney, mRNA signal is detectable at day 13 of gestation, and the protein product is observed in the ureteric bud branches. Its expression is progressively increased during later stages of the gestation extending into the neonatal periods and then is decreased in adult life. Up-regulated expression of collectrin in the hypertrophic kidneys after renal ablation and restricted spatio-temporal expression during development indicates a possible role(s) in the process of progressive renal failure and renal organogenesis.