Inversin forms a complex with catenins and N-cadherin in polarized epithelial cells
Inversin forms a complex with catenins and N-cadherin in polarized epithelial cells
复制标题
DOI：
10.1091/mbc.e02-04-0195
复制
发表时间：
2002-09-01
影响因子：
3.3
通讯作者：
Phillips, CL
中科院分区：
文献类型：
--
作者：
Nürnberger, J;Bacallao, RL;Phillips, CL
肾发生开始于两个胚胎不同的类似物，后肾间充质和输尿管芽的相互诱导。这个复杂的过程需要许多发育基因的精细和协调表达，如inv。inv基因突变的纯合子小鼠（inv/inv）会发生类似常染色体隐性遗传性多囊肾病的肾囊肿。含有inv的基因座已被提出作为一些人类和啮齿动物多囊肾病表型的常见修饰因子。我们产生了多克隆抗体inversin研究其亚细胞分布，潜在的结合伙伴，并在培养的小鼠近端小管细胞的功能方面。在细胞-细胞连接处发现了一种125 kDa的反转蛋白亚型。两个inversin亚型，140-和90-kDa，被确定在核和核周区室。质膜分配的inversin是依赖于细胞-细胞接触，并重新分配时，细胞粘附被破坏后，与低钙/EGTA培养基的细胞单层孵育。我们进一步表明，膜相关的125-kDa的逆转形成一个复杂的N-钙粘蛋白和连环蛋白。90-kDa核倒位蛋白与β-连环蛋白复合。这些发现表明inv基因产物在几个细胞区室中起作用，包括细胞核和细胞-细胞粘附位点。
Nephrogenesis starts with the reciprocal induction of two embryonically distinct analages, metanephric mesenchyme and ureteric bud. This complex process requires the refined and coordinated expression of numerous developmental genes, such as inv. Mice that are homozygous for a mutation in the inv gene (inv/inv) develop renal cysts resembling autosomal-recessive polycystic kidney disease. The gene locus containing inv has been proposed to serve as a common modifier for some human and rodent polycystic kidney disease phenotypes. We generated polyclonal antibodies to inversin to study its subcellular distribution, potential binding partners, and functional aspects in cultured murine proximal tubule cells. A 125-kDa inversin protein isoform was found at cell-cell junctions. Two inversin isoforms, 140- and 90-kDa, were identified in the nuclear and perinuclear compartments. Plasma membrane allocation of inversin is dependent upon cell-cell contacts and was redistributed when cell adhesion was disrupted after incubation of the cell monolayer with low-calcium/EGTA medium. We further show that the membrane-associated 125-kDa inversin forms a complex with N-cadherin and the catenins. The 90-kDa nuclear inversin complexes with beta-catenin. These findings indicate that the inv gene product functions in several cellular compartments, including the nucleus and cell-cell adhesion sites.