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Tubular transcytosis

Takahito Moriyama, Kazunori Karasawa, Kosaku Nitta
BACKGROUND: In the traditional theory of albuminuria, small amounts of albumin pass through the fenestrae in glomerular endothelial cells, then through the slit membrane in the gaps between foot processes of glomerular epithelial cells. In the novel theory, large amounts of albumin pass through glomerular capillaries and are taken up by megalin and cubilin receptors on tubular epithelial cells. These etiologies of urinary albumin excretion are still controversial, and the details of albumin passage through the three layers of glomerular capillaries (glomerular endothelial cells, basement membrane, and epithelial cells) have never been entirely elucidated...
2018: Contributions to Nephrology
Erin E Olsan, Tamami Matsushita, Mina Rezaei, Thomas Weimbs
Autosomal-dominant polycystic kidney disease (ADPKD) is a common life-threatening genetic disease that leads to renal failure. No treatment is available yet to effectively slow disease progression. Renal cyst growth is, at least in part, driven by the presence of growth factors in the lumens of renal cysts, which are enclosed spaces lacking connections to the tubular system. We have shown previously shown that IL13 in cyst fluid leads to aberrant activation of STAT6 via the IL4/13 receptor. Although antagonistic antibodies against many of the growth factors implicated in ADPKD are already available, they are IgG isotype antibodies that are not expected to gain access to renal cyst lumens...
June 19, 2015: Journal of Biological Chemistry
Stefanie Fruhwürth, Margit Pavelka, Robert Bittman, Werner J Kovacs, Katharina M Walter, Clemens Röhrl, Herbert Stangl
AIM: To describe the way stations of high-density lipoprotein (HDL) uptake and its lipid exchange in endothelial cells in vitro and in vivo. METHODS: A combination of fluorescence microscopy using novel fluorescent cholesterol surrogates and electron microscopy was used to analyze HDL endocytosis in great detail in primary human endothelial cells. Further, HDL uptake was quantified using radio-labeled HDL particles. To validate the in vitro findings mice were injected with fluorescently labeled HDL and particle uptake in the liver was analyzed using fluorescence microscopy...
November 26, 2013: World Journal of Biological Chemistry
Erik I Christensen, Henrik Birn
In a recent study using transgenic mice with inducible podocyte-specific expression of tagged albumin, Tenten and colleagues report transtubular transport of albumin, possibly mediated by the neonatal Fc receptor. This study raises several questions about the physiological importance of this potential pathway and the implications for albuminuria in renal disease.
December 2013: Nature Reviews. Nephrology
Verena Tenten, Sylvia Menzel, Uta Kunter, Eva-Maria Sicking, Claudia R C van Roeyen, Silja K Sanden, Michaela Kaldenbach, Peter Boor, Astrid Fuss, Sandra Uhlig, Regina Lanzmich, Brigith Willemsen, Henry Dijkman, Martin Grepl, Klemens Wild, Wilhelm Kriz, Bart Smeets, Jürgen Floege, Marcus J Moeller
Under physiologic conditions, significant amounts of plasma protein pass the renal filter and are reabsorbed by proximal tubular cells, but it is not clear whether the endocytosed protein, particularly albumin, is degraded in lysosomes or returned to the circulatory system intact. To resolve this question, a transgenic mouse with podocyte-specific expression of doxycycline-inducible tagged murine albumin was developed. To assess potential glomerular backfiltration, two types of albumin with different charges were expressed...
December 2013: Journal of the American Society of Nephrology: JASN
Ruben M Sandoval, Bruce A Molitoris
Kidney diseases involving urinary loss of large essential macromolecules, such as serum albumin, have long been thought to be caused by alterations in the permeability barrier comprised of podocytes, vascular endothelial cells, and a basement membrane working in unison. Data from our laboratory using intravital 2-photon microscopy revealed a more permeable glomerular filtration barrier (GFB) than previously thought under physiologic conditions, with retrieval of filtered albumin occurring in an early subset of cells called proximal tubule cells (PTC)(1,2,3)...
2013: Journal of Visualized Experiments: JoVE
Ruben M Sandoval, Mark C Wagner, Monica Patel, Silvia B Campos-Bilderback, George J Rhodes, Exing Wang, Sarah E Wean, Sherry S Clendenon, Bruce A Molitoris
Different laboratories recently reported incongruous results describing the quantification of albumin filtration using two-photon microscopy. We investigated the factors that influence the glomerular sieving coefficient for albumin (GSC(A)) in an effort to explain these discordant reports and to develop standard operating procedures for determining GSC(A). Multiple factors influenced GSC(A), including the kidney depth of image acquisition (10-20 μm was appropriate), the selection of fluorophore (probes emitting longer wavelengths were superior), the selection of plasma regions for fluorescence measurements, the size and molecular dispersion characteristics of dextran polymers if used, dietary status, and the genetic strain of rat...
March 2012: Journal of the American Society of Nephrology: JASN
Jakub Gburek, Krzysztof Gołąb, Katarzyna Juszczyńska
Albumin is the main protein of blood plasma, lymph, cerebrospinal fluid and interstitial fluid. The protein assists in many important body functions, including maintenance of proper colloidal osmotic pressure, transport of important metabolites and antioxidant action. Synthesis of albumin takes place mainly in the liver, and its catabolism occurs mostly in vascular endothelium of muscle, skin and liver as well as in the kidney tubular epithelium. Renal catabolism of albumin consists of glomerular filtration and tubular reabsorption...
2011: Postȩpy Higieny i Medycyny Doświadczalnej
Wanzhong He, Mark S Ladinsky, Kathryn E Huey-Tubman, Grant J Jensen, J Richard McIntosh, Pamela J Björkman
The neonatal Fc receptor (FcRn) transports maternal IgG across epithelial barriers, thereby providing the fetus or newborn with humoral immunity before its immune system is fully functional. In newborn rats, FcRn transfers IgG from milk to blood by apical-to-basolateral transcytosis across intestinal epithelial cells. The pH difference between the apical (pH 6.0-6.5) and basolateral (pH 7.4) sides of intestinal epithelial cells facilitates the efficient unidirectional transport of IgG, because FcRn binds IgG at pH 6...
September 25, 2008: Nature
Nicole A Ducharme, Janice A Williams, Asli Oztan, Gerard Apodaca, Lynne A Lapierre, James R Goldenring
Transcytosis through the apical recycling system of polarized cells is regulated by Rab11a and a series of Rab11a-interacting proteins. We have identified a point mutant in Rab11 family interacting protein 2 (Rab11-FIP2) that alters the function of Rab11a-containing trafficking systems. Rab11-FIP2(S229A/R413G) or Rab11-FIP2(R413G) cause the formation of a tubular cisternal structure containing Rab11a and decrease the rate of polymeric IgA transcytosis. The R413G mutation does not alter Rab11-FIP interactions with any known binding partners...
September 2007: American Journal of Physiology. Cell Physiology
Raquel Fantin Domeniconi, Antonio Marcos Orsi, Célia Cristina Leme Beu, Sérgio Luis Felisbino
Principal cells of the ducts epididymis of the Mongolian gerbil showed ultrastructural characteristics of lining epithelium cells close related to processes of protein secretion, and transcytosis occurring between adjacent principal cells which were mainly verified in the initial segment. Principal cells also presented roles of fluid phase and adsorptive endocytoses, as well as autophagic and heterophagic lysosomal activities mainly observed in the caput epididymis. Columnar (principal) cells of the corpus epididymidis presented great number of variable vesicles and vacuoles distributed in all the cytoplasmic levels occurring a progressive coalescence pattern among them, which help to guarantee formation of cytoplasmic channels for fluid phase transport between the tubular lumen and epididymal interstitium...
February 2007: Tissue & Cell
Permsin Marbet, Christoph Rahner, Bruno Stieger, Lukas Landmann
In order to demonstrate the power of quantitative microscopy, the endocytic apparatus of rat hepatocytes was reexamined using in situ liver and short term cultured hepatocyte couplets that were allowed to internalize endocytic markers for various time intervals. Correlative confocal light and electron microscopy demonstrate a tubulovesicular reticulum representing the endocytic apparatus. Volume and membrane area account for 2% of cell volume and 30% plasma membrane surface. Colocalization analysis demonstrated that pathway-specific ligands and fluid-phase markers enter EEA1-positive vesicles, the early endosomal compartment, immediately after internalization...
September 2006: Microscopy Research and Technique
C Reinbold, E Herrbach, V Brault
Members of the family Luteoviridae ('luteovirids') rely strictly on aphid vectors for plant-to-plant transmission. This interaction operates according to a persistent and circulative manner, which implies that the virions are being endocytosed and exocytosed across two epithelial barriers (alimentary tract and accessory salivary glands) in the vector's body. In several luteovirid-aphid vector species combinations, the route of virions in the insect has been investigated ultrastructurally by transmission electron microscopy (TEM)...
December 2003: Journal of General Virology
Touria Seddiki, Serge Delpal, Alain Aubourg, Georges Durand, Michele Ollivier-Bousquet
Plasma-borne prolactin is carried from blood to milk by transcytosis across the mammary epithelial cell through the endocytic and secretory pathways. To determine the precise route of prolactin endocytosis, intracellular transport of biotinylated prolactin was monitored, in parallel with endocytosis of fluorescein isothiocyanate-conjugated dextran and IgG, by using pulse-chase experiments in lactating mammary fragments and in enzymatically dissociated acini. Biotinylated prolactin was sorted to vesiculo-tubular organelles whereas dextran was very rapidly carried to the lumen and IgG remained accumulated in the basal region of cells...
June 2002: Biology of the Cell
Noriyoshi Kobayashi, Yusuke Suzuki, Toshinao Tsuge, Ko Okumura, Chisei Ra, Yasuhiko Tomino
In the kidney, proteins filtered through glomeruli are reabsorbed by endocytosis along the proximal tubules to avoid renal loss of large amounts of proteins. Recently, neonatal Fc receptor (FcRn), which is involved in the transport of IgG across several epithelial and endothelial cells, was reported to be expressed in renal proximal tubular epithelial cells (RPTECs). However, there has been no direct evidence for receptor-mediated endocytosis of IgG in human RPTECs. To explore physiological roles of FcRn in the proximal tubules, we used the human RPTECs to examine IgG transport...
February 2002: American Journal of Physiology. Renal Physiology
L Megias, C Guerri, E Fornas, I Azorin, E Bendala, M Sancho-Tello, J M Durán, M Tomás, M J Gomez-Lechon, J Renau-Piqueras
Endocytosis constitutes an essential process in the regulation of the expression of cell surface molecules and receptors and, therefore, could participate in the neural-glial interactions occurring during brain development. However, the relationship between endocytic pathways in astroglial cells under physiological and pathological conditions remains poorly understood. We analyzed the endocytosis and transcytosis processes in growing astrocytes and the possible effect of ethanol on these processes. Evidence demonstrates that ethanol affects endocytosis in the liver and we showed that ethanol exposure during brain development alters astroglial development changing plasma membrane receptors and surface glycoprotein composition...
February 2000: International Journal of Developmental Biology
J P Haymann, J P Levraud, S Bouet, V Kappes, J Hagège, G Nguyen, Y Xu, E Rondeau, J D Sraer
The binding of Fc fragments of Ig on glomerular epithelial cells (GEC) was observed previously, but the receptor could not be identified. In immunofluorescence and immunohistochemical studies using normal adult human kidney sections, the presence of the so-called neonatal Fc receptor (FcRn) was demonstrated on GEC as well as in the brush border of proximal tubular cells. FcRn transcripts were also detected on isolated glomeruli by reverse transcription-PCR. Using an immortalized GEC line, the presence of the FcRn was confirmed by flow cytometry, reverse transcription-PCR, Western blotting, and by the pH dependence of the binding of heat-aggregated IgG...
April 2000: Journal of the American Society of Nephrology: JASN
M Calvo, A Pol, A Lu, D Ortega, M Pons, J Blasi, C Enrich
The endocytic compartment of polarized cells is organized in basolateral and apical endosomes plus those endocytic structures specialized in recycling and transcytosis, which are still poorly characterized. The complexity of the various populations of endosomes has been demonstrated by the exquisite repertoire of endogenous proteins. In this study we examined the distribution of cellubrevin in the endocytic compartment of hepatocytes, since its intracellular location and function in polarized cells are largely unknown...
March 17, 2000: Journal of Biological Chemistry
M Maurice, N Rajho Meerson, V Bello, G Trugnan, T Ait Slimane
Type I phosphodiesterases are differently expressed by different cell types. Three members have been identified, PC-1, B10 and autotaxin. They are between 40 and 50% identical at the amino acid sequence level. Hepatocytes express both B10 and PC-1 at their plasma membrane. However, B10 is exclusively expressed at the apical pole whereas PC-1 is located at the basolateral pole. Studies of the biosynthetic route of B10 in hepatocytes shows that B10 is first transported to the basolateral surface and secondarily reaches the basolateral surface...
1999: Journal de la Société de Biologie
I Hemery, A M Durand-Schneider, G Feldmann, J P Vaerman, M Maurice
In hepatocytes, newly synthesized apical plasma membrane proteins are first delivered to the basolateral surface and are supposed to reach the apical surface by transcytosis. The transcytotic pathway of apical membrane proteins and its relationship with other endosomal pathways has not been demonstrated morphologically. We compared the intracellular route of an apical plasma membrane protein, B10, with that of polymeric IgA (pIgA), which is transcytosed, transferrin (Tf) which is recycled, and asialoorosomucoid (ASOR) which is delivered to lysosomes...
June 1996: Journal of Cell Science
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