Conditional Myh9 and Myh10 inactivation in adult mouse renal epithelium results in progressive kidney disease. Journal Article

Local Library Link: Find It @ Loyola

Authors: Otterpohl, KL; Busselman, BW; Ratnayake, I; Hart, RG; Hart, K; Evans, C; Phillips, CL; Beach, JR; Ahrenkiel, P; Molitoris, B; Surendran, K; Chandrasekar, I
Article Title: Conditional Myh9 and Myh10 inactivation in adult mouse renal epithelium results in progressive kidney disease.
Abstract: Actin-associated nonmuscle myosin II (NM2) motor proteins play critical roles in a myriad of cellular functions including endocytosis and organelle transport pathways. Cell type-specific expression and unique subcellular localization of the NM2 proteins, encoded by the Myh9 and Myh10 genes, in the mouse kidney tubules led us to hypothesize that these proteins have specialized functional roles within the renal epithelium. Inducible, conditional knockout (cKO) of Myh9 and Myh10 in the renal tubules of adult mice resulted in progressive kidney disease. Prior to overt renal tubular injury, we observed intracellular accumulation of the GPI-anchored protein uromodulin and gradual loss of Na+ K+ 2Cl- cotransporter from the apical membrane of the thick ascending limb (TAL) epithelia. The UMOD accumulation coincided with expansion of endoplasmic reticulum (ER) tubules, activation of ER stress and unfolded protein response pathways in Myh910 cKO kidneys. We conclude that NM2 proteins are required for localization and transport of UMOD and loss of function results in accumulation of UMOD and ER stress mediated progressive renal tubulointerstitial disease. These observations establish cell type-specific role(s) for NM2 proteins in regulation of specialized renal epithelial transport pathways and reveal the possibility that human kidney disease associated with MYH9 mutations could be of renal epithelial origin..
Journal Title: JCI insight
Publisher: Unknown  
Date Published: 2020