Vasohibin-1 has α-tubulin detyrosinating activity in glomerular podocytes
| Autor: | Tomoyo Mifune, Katsuyuki Tanabe, Yuri Nakashima, Satoshi Tanimura, Hitoshi Sugiyama, Yasufumi Sato, Jun Wada |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Male
Mice Knockout Podocytes Homozygote Kidney Glomerulus Biophysics Cell Cycle Proteins Cell Differentiation Cell Biology macromolecular substances urologic and male genital diseases Biochemistry Microtubules Mice Inbred C57BL Vasohibin-1 Tubulin Detyrosination Animals Humans Tyrosine Molecular Biology Cells Cultured |
| Zdroj: | Biochemical and biophysical research communications. 599 |
| ISSN: | 1090-2104 |
| Popis: | Podocytes are highly specialized epithelial cells in glomeruli, with a complex morphology composed of a cell body, primary processes, and foot processes, which maintain barrier function in glomerular filtration. The microtubule-based cytoskeleton is necessary for podocyte morphology. Microtubule structure and function can be affected by post-translational modification of tubulin, including detyrosination. Recent studies have shown that vasohibin-1 (VASH1), an antiangiogenic factor, has tubulin carboxypeptidase activity that causes detyrosination of α-tubulin. We aimed to examine the role of VASH1 in regulating α-tubulin detyrosination in podocytes and the potential involvement of VASH1 deficiency in renal morphology. In normal mouse kidneys, detyrosinated α-tubulin was mainly identified in glomeruli, especially in podocytes; meanwhile, in cultured immortalized podocytes, α-tubulin detyrosination was promoted with cell differentiation. Notably, α-tubulin detyrosination in glomeruli was diminished in Vash1 homozygous knockout (Vash1−/−) mice, and knockdown of VASH1 in cultured podocytes prevented α-tubulin detyrosination. Although VASH1 deficiency-induced downregulation of detyrosination caused no remarkable glomerular lesions, urinary albuminuria excretion and glomerular volume were significantly higher in Vash1−/− mice than in wild-type mice. Furthermore, decreased glomerular nephrin expression and narrower slit diaphragms width were observed in Vash1−/− mice. Taken together, we demonstrated that α-tubulin detyrosination in podocytes was mainly regulated by VASH1 and that VASH1 deficiency-mediated decreases in α-tubulin detyrosination led to minor alterations in podocyte morphology and predisposition to albuminuria. VASH1 expression and α-tubulin detyrosination may be novel targets for maintaining glomerular filtration barrier integrity. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect