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Proximal tubule apical endocytosis is modulated by fluid shear stress via an mTOR-dependent pathway

Cells lining the proximal tubule (PT) have unique membrane specializations that are required to maintain the high-capacity ion transport and endocytic functions of this nephron segment. PT cells in vivo acutely regulate ion transport in response to changes in glomerular filtration rate (GFR) to main...

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Autores principales: Long, Kimberly R., Shipman, Katherine E., Rbaibi, Youssef, Menshikova, Elizabeth V., Ritov, Vladimir B., Eshbach, Megan L., Jiang, Yu, Jackson, Edwin K., Baty, Catherine J., Weisz, Ora A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5597323/
https://www.ncbi.nlm.nih.gov/pubmed/28720662
http://dx.doi.org/10.1091/mbc.E17-04-0211
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author Long, Kimberly R.
Shipman, Katherine E.
Rbaibi, Youssef
Menshikova, Elizabeth V.
Ritov, Vladimir B.
Eshbach, Megan L.
Jiang, Yu
Jackson, Edwin K.
Baty, Catherine J.
Weisz, Ora A.
author_facet Long, Kimberly R.
Shipman, Katherine E.
Rbaibi, Youssef
Menshikova, Elizabeth V.
Ritov, Vladimir B.
Eshbach, Megan L.
Jiang, Yu
Jackson, Edwin K.
Baty, Catherine J.
Weisz, Ora A.
author_sort Long, Kimberly R.
collection PubMed
description Cells lining the proximal tubule (PT) have unique membrane specializations that are required to maintain the high-capacity ion transport and endocytic functions of this nephron segment. PT cells in vivo acutely regulate ion transport in response to changes in glomerular filtration rate (GFR) to maintain glomerulotubular balance. PT cells in culture up-regulate endocytic capacity in response to acute changes in fluid shear stress (FSS); however, it is not known whether GFR modulates PT endocytosis to enable maximally efficient uptake of filtered proteins in vivo. Here, we show that cells cultured under continuous FSS develop an expanded apical endocytic pathway and increased endocytic capacity and lysosomal biogenesis. Furthermore, endocytic capacity in fully differentiated cells is rapidly modulated by changes in FSS. PT cells exposed to continuous FSS also acquired an extensive brush border and basolateral membrane invaginations resembling those observed in vivo. Culture under suboptimal levels of FSS led to intermediate phenotypes, suggesting a threshold effect. Cells exposed to FSS expressed higher levels of key proteins necessary for PT function, including ion transporters, receptors, and membrane-trafficking machinery, and increased adenine nucleotide levels. Inhibition of the mechanistic target of rapamycin (mTOR) using rapamycin prevented the increase in cellular energy levels, lysosomal biogenesis, and endocytic uptake, suggesting that these represent a coordinated differentiation program. In contrast, rapamycin did not prevent the FSS-induced increase in Na(+)/K(+)-ATPase levels. Our data suggest that rapid tuning of the endocytic response by changes in FSS may contribute to glomerulotubular balance in vivo. Moreover, FSS provides an essential stimulus in the differentiation of PT cells via separate pathways that up-regulate endocytosis and ion transport capacity. Variations in FSS may also contribute to the maturation of PT cells during kidney development and during repair after kidney injury.
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spelling pubmed-55973232017-11-30 Proximal tubule apical endocytosis is modulated by fluid shear stress via an mTOR-dependent pathway Long, Kimberly R. Shipman, Katherine E. Rbaibi, Youssef Menshikova, Elizabeth V. Ritov, Vladimir B. Eshbach, Megan L. Jiang, Yu Jackson, Edwin K. Baty, Catherine J. Weisz, Ora A. Mol Biol Cell Articles Cells lining the proximal tubule (PT) have unique membrane specializations that are required to maintain the high-capacity ion transport and endocytic functions of this nephron segment. PT cells in vivo acutely regulate ion transport in response to changes in glomerular filtration rate (GFR) to maintain glomerulotubular balance. PT cells in culture up-regulate endocytic capacity in response to acute changes in fluid shear stress (FSS); however, it is not known whether GFR modulates PT endocytosis to enable maximally efficient uptake of filtered proteins in vivo. Here, we show that cells cultured under continuous FSS develop an expanded apical endocytic pathway and increased endocytic capacity and lysosomal biogenesis. Furthermore, endocytic capacity in fully differentiated cells is rapidly modulated by changes in FSS. PT cells exposed to continuous FSS also acquired an extensive brush border and basolateral membrane invaginations resembling those observed in vivo. Culture under suboptimal levels of FSS led to intermediate phenotypes, suggesting a threshold effect. Cells exposed to FSS expressed higher levels of key proteins necessary for PT function, including ion transporters, receptors, and membrane-trafficking machinery, and increased adenine nucleotide levels. Inhibition of the mechanistic target of rapamycin (mTOR) using rapamycin prevented the increase in cellular energy levels, lysosomal biogenesis, and endocytic uptake, suggesting that these represent a coordinated differentiation program. In contrast, rapamycin did not prevent the FSS-induced increase in Na(+)/K(+)-ATPase levels. Our data suggest that rapid tuning of the endocytic response by changes in FSS may contribute to glomerulotubular balance in vivo. Moreover, FSS provides an essential stimulus in the differentiation of PT cells via separate pathways that up-regulate endocytosis and ion transport capacity. Variations in FSS may also contribute to the maturation of PT cells during kidney development and during repair after kidney injury. The American Society for Cell Biology 2017-09-15 /pmc/articles/PMC5597323/ /pubmed/28720662 http://dx.doi.org/10.1091/mbc.E17-04-0211 Text en © 2017 Long et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology.
spellingShingle Articles
Long, Kimberly R.
Shipman, Katherine E.
Rbaibi, Youssef
Menshikova, Elizabeth V.
Ritov, Vladimir B.
Eshbach, Megan L.
Jiang, Yu
Jackson, Edwin K.
Baty, Catherine J.
Weisz, Ora A.
Proximal tubule apical endocytosis is modulated by fluid shear stress via an mTOR-dependent pathway
title Proximal tubule apical endocytosis is modulated by fluid shear stress via an mTOR-dependent pathway
title_full Proximal tubule apical endocytosis is modulated by fluid shear stress via an mTOR-dependent pathway
title_fullStr Proximal tubule apical endocytosis is modulated by fluid shear stress via an mTOR-dependent pathway
title_full_unstemmed Proximal tubule apical endocytosis is modulated by fluid shear stress via an mTOR-dependent pathway
title_short Proximal tubule apical endocytosis is modulated by fluid shear stress via an mTOR-dependent pathway
title_sort proximal tubule apical endocytosis is modulated by fluid shear stress via an mtor-dependent pathway
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5597323/
https://www.ncbi.nlm.nih.gov/pubmed/28720662
http://dx.doi.org/10.1091/mbc.E17-04-0211
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