The Rho GAP Myosin IXa is a regulator of kidney tubule function.

In this study, we report that Myo9a-deficient mice develop bilateral renal disease, characterized by dilation of proximal tubules, calyceal dilation, thinning of the parenchyma and fibrosis. These structural changes are accompanied by polyuria (with normal vasopressin levels) and low molecular weight proteinuria. Immunohistochemistry revealed that Myo9a is localized to the circumferential F-actin belt of proximal tubule cells. In kidneys lacking Myo9a, the multiligand binding receptor megalin and its ligand albumin accumulated at the luminal surface of Myo9a-/- proximal tubular cells, suggesting that endocytosis is dysregulated. In addition, we found, surprisingly, that levels of the formin mDia1, a Rho effector, were decreased in Myo9a-/- kidneys, as well as in Myo9a knockdown LLC-PK1 cells. In summary, deletion of the RhoGAP Myo9a in mice causes proximal tubular dilation and fibrosis, and we speculate that downregulation of mDia1 and impaired protein reabsorption contribute to the pathophysiology. PMID: 26136556 [PubMed - as supplied by publisher]
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research