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1Polesel M, 1Schuh CD, 1,2Hänni D, 2Kirschmann M, 2Mateos JM 2Käch A, 1Hall AM (1Structural & Functional Imaging Group, Institute of Anatomy, University of Zurich, Switzerland 2Center for Microscopy and Image Analysis, University of Zurich, Switzerland)
Blood low molecular weight proteins (LMWP) are filtered in the kidney glomeruli and subsequently reabsorbed via receptor-mediated endocytosis (RME) in the proximal convoluted tubule (PCT). After RME, the destiny of LMWP that enter the endo-lysosomal system (ELS) is to either be degraded in lysosomes or recycled to the blood stream via transcytosis. The PCT is divided into early and late segments (S1 and S2, respectively), based on differences observed with electron microscopy (EM). We recently found that RME of LMWPs takes place exclusively in S1 (JASN 2018). The aim of this study was to investigate how the structure of the ELS in S1 cells is adapted to this purpose. To gain deeper insights into the micro-anatomical features responsible for the greater capacity of LMWP reabsorption in S1, we performed high resolution volume imaging using focused ion beam-scanning EM and acquired sections through the entire thickness of an S1 cell. Using a machine-learning based approach, we segmented the different components of the ELS and rebuilt their 3-D appearance. Taken together, our findings have important implications for understanding reabsorption of LMWP in the PCT in vivo.