Role of c-Abl and nephrin in podocyte cytoskeletal remodeling induced by angiotensin II.
Cell Death Dis
; 9(2): 185, 2018 02 07.
Article
em En
| MEDLINE
| ID: mdl-29416010
ABSTRACT
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Angiotensina II
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Proteínas Proto-Oncogênicas c-abl
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Podócitos
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Proteínas de Membrana
Limite:
Adult
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Animals
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Cell Death Dis
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
China