We show that the expression and localization of the CMA receptor, LAMP2A, is defective in CTNS-KO PTCs. Here, using CRISPR-Cas9 technology, we develop a new human PTC line with defective cystinosin expression ( CTNS-KO PTCs). Chaperone-mediated autophagy (CMA), a selective form of autophagy, is defective in cystinotic mouse fibroblasts, and treatment with cysteamine is unable to correct CMA defects in vivo, but whether the vesicular trafficking mechanisms that lead to defective CMA in cystinosis are manifested in human PTCs is not currently known and whether PTC-specific mechanisms are corrected upon CMA upregulation remains to be elucidated. Kidney disease is developed despite the use of cysteamine, a drug that decreases lysosomal cystine overload but fails to correct overload-independent defects. Patients with nephropathic cystinosis are characterized by endocrine defects, defective proximal tubule cell (PTC) function, the development of Fanconi syndrome and, eventually, end-stage renal disease. 3Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, NY, United StatesĬystinosis is a lysosomal storage disorder caused by defects in CTNS, the gene that encodes the lysosomal cystine transporter cystinosin.2Department of Biochemistry, Albert Einstein College of Medicine, Bronx, NY, United States.1Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA, United States. ![]() Johnson 1, Farhana Rahman 1, Evripidis Gavathiotis 2, Ana Maria Cuervo 3 and Sergio D.
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