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Int. J. Mol. Sci. 2018, 19(2), 479; doi:10.3390/ijms19020479

The Role of Trio, a Rho Guanine Nucleotide Exchange Factor, in Glomerular Podocytes

1
Division of Experimental Medicine, McGill University, Montreal, QC H3A 0G4, Canada
2
Division of Nephrology, McGill University Health Centre, Montreal, QC H4A 3J1, Canada
*
Author to whom correspondence should be addressed.
Received: 19 December 2017 / Revised: 3 February 2018 / Accepted: 3 February 2018 / Published: 6 February 2018
(This article belongs to the Special Issue Small GTPases)
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Abstract

Nephrotic syndrome is a kidney disease featured by heavy proteinuria. It is caused by injury to the specialized epithelial cells called “podocytes” within the filtration unit of the kidney, glomerulus. Previous studies showed that hyperactivation of the RhoGTPase, Rac1, in podocytes causes podocyte injury and glomerulosclerosis (accumulation of extracellular matrix in the glomerulus). However, the mechanism by which Rac1 is activated during podocyte injury is unknown. Trio is a guanine nucleotide exchange factor (GEF) known to activate Rac1. By RNA-sequencing, we found that Trio mRNA is abundantly expressed in cultured human podocytes. Trio mRNA was also significantly upregulated in humans with minimal change disease and focal segmental glomerulosclerosis, two representative causes of nephrotic syndrome. Reduced expression of Trio in cultured human podocytes decreased basal Rac1 activity, cell size, attachment to laminin, and motility. Furthermore, while the pro-fibrotic cytokine, transforming growth factor β1 increased Rac1 activity in control cells, it decreases Rac1 activity in cells with reduced Trio expression. This was likely due to simultaneous activation of the Rac1-GTPase activation protein, CdGAP. Thus, Trio is important in the basal functions of podocytes and may also contribute to glomerular pathology, such as sclerosis, via Rac1 activation. View Full-Text
Keywords: Trio; CdGAP; Rac1; podocytes; focal segmental glomerulosclerosis; nephrotic syndrome; transforming growth factor β1 Trio; CdGAP; Rac1; podocytes; focal segmental glomerulosclerosis; nephrotic syndrome; transforming growth factor β1
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MDPI and ACS Style

Maier, M.; Baldwin, C.; Aoudjit, L.; Takano, T. The Role of Trio, a Rho Guanine Nucleotide Exchange Factor, in Glomerular Podocytes. Int. J. Mol. Sci. 2018, 19, 479.

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