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

摘要: Cells lining the proximal tubule (PT) have unique membrane specializations that are required to maintain high-capacity ion transport and endocytic functions of this nephron segment. PT cells in vivo acutely regulate response changes glomerular filtration rate (GFR) glomerulotubular balance. culture up-regulate capacity acute fluid shear stress (FSS); however, it is not known whether GFR modulates endocytosis enable maximally efficient uptake filtered proteins vivo. Here, we show cultured under continuous FSS develop an expanded apical pathway increased lysosomal biogenesis. Furthermore, fully differentiated rapidly modulated by FSS. exposed also acquired extensive brush border basolateral invaginations resembling those observed Culture suboptimal levels led intermediate phenotypes, suggesting a threshold effect. expressed higher key necessary for function, including transporters, receptors, membrane-trafficking machinery, adenine nucleotide levels. Inhibition mechanistic target rapamycin (mTOR) using prevented increase cellular energy levels, biogenesis, uptake, these represent coordinated differentiation program. In contrast, did prevent FSS-induced Na+/K+-ATPase Our data suggest rapid tuning may contribute balance Moreover, provides essential stimulus via separate pathways capacity. Variations maturation during kidney development repair after injury.