EphB2 and ephrin-B1 expressed in the adult kidney regulate the cytoarchitecture of medullary tubule cells through Rho family GTPases
EphB2 and ephrin-B1 expressed in the adult kidney regulate the cytoarchitecture of medullary tubule cells through Rho family GTPases
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DOI：
10.1242/jcs.02777
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发表时间：
2006-02-01
影响因子：
4
通讯作者：
Tsuyama, S
中科院分区：
文献类型：
--
作者：
Ogawa, K;Wada, H;Tsuyama, S
Eph受体和ephrin配体是膜结合的细胞间通讯分子，在发育过程中具有明确的功能，但它们在许多成人组织中的表达模式和功能仍然是未知的。我们已经通过RT-PCR扩增在成年小鼠肾脏中检测到EphB 2和EphB 6受体以及肝配蛋白-BI配体的实质水平。免疫定位实验显示EphB 2定位于内、外髓质的小管中，EphB 6定位于外髓质和皮质的小管中。相反，肝配蛋白-B1在整个肾单位的小管中检测到。与髓质中EphB 2受体和肝配蛋白-BI配体的重叠表达一致，EphB 2在肾脏中被酪氨酸磷酸化，因此被激活。然而，在外髓质中，EphB 2信号传导可能被共表达的激酶失活的EphB 6受体减弱。有趣的是，我们发现，EphB信号诱导RhoA激活和Rac 1失活以及细胞收缩，扩大局灶性粘连和突出的应力纤维在原代培养的髓小管细胞。这些结果表明，EphB受体信号通过Rho家族GTPases调节成人肾脏髓质中小管细胞的细胞结构和空间组织，因此，可能影响肾脏的重吸收能力。
Eph receptors and ephrin ligands are membrane-bound cell-cell communication molecules with well-defined functions in development, but their expression patterns and functions in many adult tissues are still largely unknown. We have detected substantial levels of the EphB2 and EphB6 receptors and the ephrin-BI ligand in the adult mouse kidney by RT-PCR amplification. Immunolocalization experiments revealed that EphB2 is localized in the tubules of the inner and outer medulla and EphB6 is in the tubules of the outer medulla and cortex. By contrast, ephrin-B1 was detected in tubules throughout the whole nephron. Consistent with the overlapping expression of the EphB2 receptor and the ephrin-BI ligand in the medulla, EphB2 is tyrosine-phosphorylated, and therefore activated, in the kidney. In the outer medulla, however, EphB2 signaling may be attenuated by the co-expressed kinase-inactive EphB6 receptor. Interestingly, we found that EphB signaling induces RhoA activation and Rac1 inactivation as well as cell retraction, enlargement of focal adhesions and prominent stress fibers in primary cultures of medullary tubule cells. These results suggest that EphB receptor signaling through Rho family GTPases regulates the cytoarchitecture and spatial organization of the tubule cells in the adult kidney medulla and, therefore, may affect the reabsorption ability of the kidney.