The search result changed since you submitted your search request. Documents might be displayed in a different sort order.
  • search hit 24 of 147
Back to Result List

mTOR Regulates Endocytosis and Nutrient Transport in Proximal Tubular Cells

  • Renal proximal tubular cells constantly recycle nutrients to ensure minimal loss of vital substrates into the urine. Although most of the transport mechanisms have been discovered at the molecular level, little is known about the factors regulating these processes. Here, we show that mTORC1 and mTORC2 specifically and synergistically regulate PTC endocytosis and transport processes. Using a conditional mouse genetic approach to disable nonredundant subunits of mTORC1, mTORC2, or both, we showed that mice lacking mTORC1 or mTORC1/mTORC2 but not mTORC2 alone develop a Fanconi-like syndrome of glucosuria, phosphaturia, aminoaciduria, low molecular weight proteinuria, and albuminuria. Interestingly, proteomics and phosphoproteomics of freshly isolated kidney cortex identified either reduced expression or loss of phosphorylation at critical residues of different classes of specific transport proteins. Functionally, this resulted in reduced nutrient transport and a profound perturbation of the endocytic machinery, despite preserved absolute expression of the main scavenger receptors, MEGALIN and CUBILIN. Our findings highlight a novel mTOR–dependent regulatory network for nutrient transport in renal proximal tubular cells.

Export metadata

Additional Services

Share in Twitter Search Google Scholar Availability
Metadaten
Document Type:Article
Language:English
Parent Title (English):J Am Soc Nephrol. (Journal of the American Society of Nephrology)
Volume:28
Issue:1
First Page:230
Last Page:241
ISSN:1533-3450
DOI:https://doi.org/10.1681/ASN.2015111224
Pubmed Id:http://www.ncbi.nlm.nih.gov/pubmed?term=27297946
Publisher:American Society of Nephrology
Date of first publication:2016/06/13
Tag:albuminuria; endocytosis; epithelial transport; mTOR; proteomics; proximal tubule
Departments, institutes and facilities:Fachbereich Angewandte Naturwissenschaften
Institut für funktionale Gen-Analytik (IfGA)
Dewey Decimal Classification (DDC):5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
Entry in this database:2016/06/23