PUBLICATION
Crk1/2 and CrkL play critical roles in maintaining podocyte morphology and function
- Authors
- Du, J., Meng, L., Pang, L., Jin, B., Duan, N., Huang, C., Huang, H., Li, H.
- ID
- ZDB-PUB-200615-13
- Date
- 2020
- Source
- Experimental cell research 394(1): 112135 (Journal)
- Registered Authors
- Keywords
- Crk1/2, CrkL, Cytoskeleton, Focal adhesion, Podocyte, Zebrafish
- MeSH Terms
-
- Actin Cytoskeleton/metabolism
- Adaptor Proteins, Signal Transducing/metabolism*
- Focal Adhesion Protein-Tyrosine Kinases/metabolism
- Glomerulosclerosis, Focal Segmental/genetics
- Glomerulosclerosis, Focal Segmental/metabolism
- Humans
- Kidney Diseases/metabolism
- Kidney Glomerulus/metabolism
- Phosphatidylinositol 3-Kinase/metabolism
- Podocytes/metabolism*
- Podocytes/pathology*
- Proto-Oncogene Proteins c-crk/metabolism*
- PubMed
- 32535035 Full text @ Exp. Cell Res.
Citation
Du, J., Meng, L., Pang, L., Jin, B., Duan, N., Huang, C., Huang, H., Li, H. (2020) Crk1/2 and CrkL play critical roles in maintaining podocyte morphology and function. Experimental cell research. 394(1):112135.
Abstract
Podocytes are actin-rich epithelial cells whose effacement and detachment are the main cause of glomerular disease. Crk family proteins: Crk1/2 and CrkL are reported to be important intracellular signaling proteins that are involved in many biological processes. However, the roles of them in maintaining podocyte morphology and function remain poorly understood. In this study, specific knocking down of Crk1/2 and CrkL in podocytes caused abnormal cell morphology, actin cytoskeleton rearrangement and dysfunction in cell adhesion, spreading, migration, and viability. The p130Cas, focal adhesion kinase, phosphatidylinositol 3-kinase/Akt, p38 and JNK signaling pathways involved in these alterations. Furthermore, knocking down CrkL alone conferred a more modest phenotype than did the Crk1/2 knockdown and the double knockdown. Kidney biopsy specimens from patients with focal segmental glomerulosclerosis and minimal change nephropathy showed downregulation of Crk1/2 and CrkL in glomeruli. In zebrafish embryos, Crk1/2 and CrkL knockdown compromised the morphology and caused abnormal glomerular development. Thus, our results suggest that Crk1/2 and CrkL expression are important in podocytes; loss of either will cause podocyte dysfunction, leading to foot process effacement and podocyte detachment.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping