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Conditional Myh9 and Myh10 inactivation in adult mouse renal epithelium results in progressive kidney disease.
Otterpohl, Karla L; Busselman, Brook W; Ratnayake, Ishara; Hart, Ryan G; Hart, Kimberly R; Evans, Claire M; Phillips, Carrie L; Beach, Jordan R; Ahrenkiel, Phil; Molitoris, Bruce A; Surendran, Kameswaran; Chandrasekar, Indra.
Afiliación
  • Otterpohl KL; Enabling Technologies Group, Sanford Research, Sioux Falls, South Dakota, USA.
  • Busselman BW; Enabling Technologies Group, Sanford Research, Sioux Falls, South Dakota, USA.
  • Ratnayake I; Basic Biomedical Sciences Graduate Program, University of South Dakota, Vermillion, South Dakota, USA.
  • Hart RG; Department of Nanoscience and Nanoengineering, South Dakota School of Mines and Technology, Rapid City, South Dakota, USA.
  • Hart KR; Enabling Technologies Group, Sanford Research, Sioux Falls, South Dakota, USA.
  • Evans CM; Department of Pediatrics, University of South Dakota Sanford School of Medicine, Sioux Falls, South Dakota, USA.
  • Phillips CL; Histology and Imaging Core, Sanford Research, Sioux Falls, South Dakota, USA.
  • Beach JR; Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA.
  • Ahrenkiel P; Department of Cell and Molecular Physiology, Loyola University Chicago Stritch School of Medicine, Maywood, Illinois, USA.
  • Molitoris BA; Department of Nanoscience and Nanoengineering, South Dakota School of Mines and Technology, Rapid City, South Dakota, USA.
  • Surendran K; Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA.
  • Chandrasekar I; Department of Pediatrics, University of South Dakota Sanford School of Medicine, Sioux Falls, South Dakota, USA.
JCI Insight ; 5(21)2020 11 05.
Article en En | MEDLINE | ID: mdl-33001861
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 glycosylphosphatidylinositol-anchored protein uromodulin (UMOD) and gradual loss of Na+ K+ 2Cl- cotransporter from the apical membrane of the thick ascending limb epithelia. The UMOD accumulation coincided with expansion of endoplasmic reticulum (ER) tubules and activation of ER stress and unfolded protein response pathways in Myh9&10-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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Cadenas Pesadas de Miosina / Miosina Tipo IIB no Muscular / Epitelio / Estrés del Retículo Endoplásmico / Enfermedades Renales / Túbulos Renales Tipo de estudio: Etiology_studies Límite: Animals Idioma: En Revista: JCI Insight Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Cadenas Pesadas de Miosina / Miosina Tipo IIB no Muscular / Epitelio / Estrés del Retículo Endoplásmico / Enfermedades Renales / Túbulos Renales Tipo de estudio: Etiology_studies Límite: Animals Idioma: En Revista: JCI Insight Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos