Small and large intestine express a truncated Dab1 isoform that assembles in cell-cell junctions and co-localizes with proteins involved in endocytosis.
Small and large intestine express a truncated Dab1 isoform that assembles in cell-cell junctions and co-localizes with proteins involved in endocytosis.
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小肠和大肠表达截短的 Dab1 亚型，该亚型在细胞-细胞连接处组装，并与参与内吞作用的蛋白质共定位。
DOI：
10.1016/j.bbamem.2018.02.014
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Vázquez-Carretero MD
中科院分区：
文献类型：
--
作者：
Vázquez-Carretero MD
Disabled-1 （Dab1）是reelin通路中必不可少的细胞内接头蛋白。我们之前在小鼠肠道中的研究表明，Dab1将reelin信号传递到细胞质信号通路。在这里，我们确定了Dab1亚型在啮齿动物小肠和大肠中的表达，以及它与网格蛋白、小洞蛋白-1和N-Wasp的亚细胞定位和共定位。PCR和测序分析表明，啮齿动物小肠和大肠表达的Dab1亚型缺失了脑Dab1亚型（典型）中5个酪氨酸磷酸化位点中的3个（Y198、y200和Y220），并包含核定位和输出信号。Western blot检测显示，隐藏祖细胞的隐窝和肠细胞都表达相同的Dab1亚型，这表明上皮细胞分化并不调节Dab1变体在肠道的产生。他们还揭示了规范和肠道Dab1亚型在其总磷酸化程度上的差异。免疫染色分析显示，在肠细胞中，Dab1定位于顶端和外侧膜、顶端囊泡、粘附连接处和桥粒附近以及细胞核；在Caco-2细胞中，Dab1通过依赖Ca2+的过程定位于细胞间的连接处。综上所述，在啮齿类动物的肠道中，截断的Dab1变体传递了reelin信号，并可能在网格蛋白介导的根尖内吞作用和细胞间连接组装的控制中发挥作用。肠Dab1变异体作为核细胞质穿梭蛋白的功能也可以从其序列和核位置推断出来。
Disabled-1 (Dab1) is an essential intracellular adaptor protein in the reelin pathway. Our previous studies in mice intestine showed that Dab1 transmits the reelin signal to cytosolic signalling pathways. Here, we determine the Dab1 isoform expressed in rodent small and large intestine, its subcellular location and co-localization with clathrin, caveolin-1 and N-Wasp. PCR and sequencing analysis reveal that rodent small and large intestine express a Dab1 isoform that misses three (Y198, Y200and Y220) of the five tyrosine phosphorylation sites present in brain Dab1 isoform (canonical) and contains nuclear localization and export signals. Western blot assays show that both, crypts, which shelter progenitor cells, and enterocytes express the same Dab1 isoform, suggesting that epithelial cell differentiation does not regulate intestinal generation of alternatively spliced Dab1 variants. They also reveal that the canonical and the intestinal Dab1 isoforms differ in their total degree of phosphorylation. Immunostaining assays show that in enterocytes Dab1 localizes at the apical and lateral membranes, apical vesicles, close to adherens junctions and desmosomes, as well as in the nucleus; co-localizes with clathrin and with N-Wasp but not with caveolin-1, and in Caco-2 cells Dab1 localizes at cell-to-cell junctions by a Ca2+-dependent process. In conclusion, the results indicate that in rodent intestine a truncated Dab1 variant transmits the reelin signal and may play a role in clathrin-mediated apical endocytosis and in the control of cell-to-cell junction assembly. A function of intestinal Dab1 variant as a nucleocytoplasmic shuttling protein is also inferred from its sequence and nuclear location.
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Dab2、Megalin、Cubilin 和无羊膜受体复合物可能介导乳鼠的肠内吞作用
影响因子：
4
作者：
M. Vázquez;M. Palomo;P. García;I. Sánchez;M. J. Peral;M. L. Calonge;A. Ilundain
通讯作者：
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影响因子：
4.8
作者：
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通讯作者：
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DOI：
10.1073/pnas.97.3.1096
发表时间：
2000-02-01
影响因子：
11.1
作者：
ter Haar, E;Harrison, SC;Kirchhausen, T
通讯作者：
Kirchhausen, T
影响因子：
4.8
作者：
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通讯作者：
Curran, T