EphB2 and ephrin-B1 expressed in the adult kidney regulate the cytoarchitecture of medullary tubule cells through Rho family GTPases.
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-B1 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-B1 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.
Ogawa
Kazushige
K
Department of Veterinary Anatomy, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Sakai, Osaka 599-8531, Japan. kogawa@vet.osakafu-u.ac.jp
Wada
Hiroki
H
Okada
Noriyoshi
N
Harada
Itsuki
I
Nakajima
Takayuki
T
Pasquale
Elena B
EB
Tsuyama
Shingo
S
D000818:Animals; D036387:Ephrin-B1 / Q000096:biosynthesis*; D022001:Focal Adhesions / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology*; D007679:Kidney Medulla / Q000166:cytology / Q000378:metabolism*; D007684:Kidney Tubules / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D009479:Neuropeptides / Q000378:metabolism; D036183:Receptor, EphB2 / Q000096:biosynthesis*; D015398:Signal Transduction / Q000502:physiology*; D020744:rac GTP-Binding Proteins / Q000378:metabolism; D020830:rac1 GTP-Binding Protein; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
C092571:Efnb1 protein, mouse; D036387:Ephrin-B1; D009479:Neuropeptides; C484602:Rac1 protein, mouse; D036183:Receptor, EphB2; D020744:rac GTP-Binding Proteins; D020830:rac1 GTP-Binding Protein; D020742:rhoA GTP-Binding Protein