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10.1091/mbc.E17-04-0211 http://scihub22266oqcxt.onion/10.1091/mbc.E17-04-0211 C5597323!5597323 !28720662     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=28720662 &cmd=llinks): Failed to open stream: HTTP request failed! 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Proximal tubule apical endocytosis is modulated by fluid shear stress via an mTOR-dependent pathway |pdf=|usr=}}{{28720662 }} gab.com Text Proximal tubule apical endocytosis is modulated by fluid shear stress via an mTOR-dependent pathway JO: Mol Biol Cell http://www.kidney.de/pget.php?&tw=1&pmid=28720662 #FOAvip 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. Twit Text FOAVip Proximal tubule apical endocytosis is modulated by fluid shear stress via an mTOR-dependent pathway ????Mol Biol Cell http://www.kidney.de/pget.php?&tw=1&pmid=28720662 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=28720662 #FOAvip English Wikipedia <ref>{{Cite pmid|28720662 }}</ref> Proximal tubule apical endocytosis is modulated by fluid shear stress via an mTOR-dependent pathway #MMPMID28720662 Long KR ; Shipman KE ; Rbaibi Y ; Menshikova EV ; Ritov VB ; Eshbach ML ; Jiang Y ; Jackson EK ; Baty CJ ; Weisz OA Mol Biol Cell 2017[Sep]; 28 (19 ): 2508-2517 PMID28720662 show ga 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. |Animals [MESH] |Cell Membrane/metabolism [MESH] |Cells, Cultured [MESH] |Endocytosis [MESH] |Glomerular Filtration Rate [MESH] |Kidney Tubules, Proximal/cytology/metabolism/*physiology [MESH] |Membrane Proteins/physiology [MESH] |Metabolic Networks and Pathways [MESH] |Opossums [MESH] |Protein Transport [MESH] |Shear Strength [MESH] |Stress, Mechanical [MESH]Proximal tubule apical endocytosis is modulated by fluid shear stress (epmc).pdf DeepDyve Pubget Overpricing