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Role of c-Abl and nephrin in podocyte cytoskeletal remodeling induced by angiotensin II
Our previous study showed that angiotensin II (Ang II) exposure diminished the interaction between nephrin and c-Abl, then c-Abl mediated SHIP2-Akt pathway in the process of podocyte injury in vivo and vitro. However, the relationship between nephrin and c-Abl was unknown. Recently, various studies...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5833834/ https://www.ncbi.nlm.nih.gov/pubmed/29416010 http://dx.doi.org/10.1038/s41419-017-0225-y |
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author | Ma, Yiqiong Yang, Qian Zhong, Zhentong Liang, Wei Zhang, Lu Yang, Yingjie Ding, Guohua |
author_facet | Ma, Yiqiong Yang, Qian Zhong, Zhentong Liang, Wei Zhang, Lu Yang, Yingjie Ding, Guohua |
author_sort | Ma, Yiqiong |
collection | PubMed |
description | Our previous study showed that angiotensin II (Ang II) exposure diminished the interaction between nephrin and c-Abl, then c-Abl mediated SHIP2-Akt pathway in the process of podocyte injury in vivo and vitro. However, the relationship between nephrin and c-Abl was unknown. Recently, various studies showed that nephrin was required for cytoskeletal remodeling in glomerular podocytes. But its specific mechanisms remain incompletely understood. As a nonreceptor tyrosine kinase involved in cytoskeletal regulation, c-Abl may be a candidate of signaling proteins interacting with Src homology 2/3 (SH2/SH3) domains of nephrin. Therefore, it is proposed that c-Abl contributes to nephrin-dependent cytoskeletal remodeling of podocytes. Herein, we observed that nephrin-c-Abl colocalization were suppressed in glomeruli of patients with proteinuria. Next, CD16/7-nephrin and c-Abl vectors were constructed to investigate the nephrin-c-Abl signaling pathway in podocyte actin-cytoskeletal remodeling. The disorganized cytoskeleton stimulated by cytochalasin D in COS7 cells was dramatically restored by co-transfection with phosphorylated CD16/7-nephrin and c-Abl full-length constructs. Further, co-immunoprecipitation showed that phosphorylated CD16/7-nephrin interacted with wild-type c-Abl, but not with SH2/SH3-defective c-Abl. These findings suggest that phosphorylated nephrin is able to recruit c-Abl in a SH2/SH3-dependent manner and detached c-Abl from dephosphorylated nephrin contributes to cytoskeletal remodeling in podocytes. |
format | Online Article Text |
id | pubmed-5833834 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-58338342018-03-06 Role of c-Abl and nephrin in podocyte cytoskeletal remodeling induced by angiotensin II Ma, Yiqiong Yang, Qian Zhong, Zhentong Liang, Wei Zhang, Lu Yang, Yingjie Ding, Guohua Cell Death Dis Article Our previous study showed that angiotensin II (Ang II) exposure diminished the interaction between nephrin and c-Abl, then c-Abl mediated SHIP2-Akt pathway in the process of podocyte injury in vivo and vitro. However, the relationship between nephrin and c-Abl was unknown. Recently, various studies showed that nephrin was required for cytoskeletal remodeling in glomerular podocytes. But its specific mechanisms remain incompletely understood. As a nonreceptor tyrosine kinase involved in cytoskeletal regulation, c-Abl may be a candidate of signaling proteins interacting with Src homology 2/3 (SH2/SH3) domains of nephrin. Therefore, it is proposed that c-Abl contributes to nephrin-dependent cytoskeletal remodeling of podocytes. Herein, we observed that nephrin-c-Abl colocalization were suppressed in glomeruli of patients with proteinuria. Next, CD16/7-nephrin and c-Abl vectors were constructed to investigate the nephrin-c-Abl signaling pathway in podocyte actin-cytoskeletal remodeling. The disorganized cytoskeleton stimulated by cytochalasin D in COS7 cells was dramatically restored by co-transfection with phosphorylated CD16/7-nephrin and c-Abl full-length constructs. Further, co-immunoprecipitation showed that phosphorylated CD16/7-nephrin interacted with wild-type c-Abl, but not with SH2/SH3-defective c-Abl. These findings suggest that phosphorylated nephrin is able to recruit c-Abl in a SH2/SH3-dependent manner and detached c-Abl from dephosphorylated nephrin contributes to cytoskeletal remodeling in podocytes. Nature Publishing Group UK 2018-02-07 /pmc/articles/PMC5833834/ /pubmed/29416010 http://dx.doi.org/10.1038/s41419-017-0225-y Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Ma, Yiqiong Yang, Qian Zhong, Zhentong Liang, Wei Zhang, Lu Yang, Yingjie Ding, Guohua Role of c-Abl and nephrin in podocyte cytoskeletal remodeling induced by angiotensin II |
title | Role of c-Abl and nephrin in podocyte cytoskeletal remodeling induced by angiotensin II |
title_full | Role of c-Abl and nephrin in podocyte cytoskeletal remodeling induced by angiotensin II |
title_fullStr | Role of c-Abl and nephrin in podocyte cytoskeletal remodeling induced by angiotensin II |
title_full_unstemmed | Role of c-Abl and nephrin in podocyte cytoskeletal remodeling induced by angiotensin II |
title_short | Role of c-Abl and nephrin in podocyte cytoskeletal remodeling induced by angiotensin II |
title_sort | role of c-abl and nephrin in podocyte cytoskeletal remodeling induced by angiotensin ii |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5833834/ https://www.ncbi.nlm.nih.gov/pubmed/29416010 http://dx.doi.org/10.1038/s41419-017-0225-y |
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