D Brown

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..We propose that the 'polarity reversal' of the H(+)V-ATPase in B-intercalated cells is mediated by a physiologically regulated transcytotic pathway that may be similar to that existing in some other cell types...

..Examples of these events in renal epithelial cells are highlighted throughout this review and are related to the physiology of the kidney...

..This review emphasizes important structural and functional features of proton-secreting cells, describes the tissue distribution of these cells and discusses the known functions of these cells in their respective epithelia...

..In some cases, the mutated protein is retained and degraded intracellularly, while in others it may not be delivered to the cell surface after the appropriate physiological stimulation...

..Understanding cAMP-independent mechanisms for membrane insertion of AQP2 is especially relevant to the therapeutic bypassing of the mutated, dysfunctional vasopressin receptor in patients with X-linked nephrogenic diabetes insipidus...

..This review briefly introduces and discusses some of the systems and methodologies that are available from several manufacturers, including laser scanning and spinning disk confocal microscopy, and total internal reflectance microscopy...

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..The complexes that are shed in Heymann nephritis contain either a portion of gp330 cleaved from the full-length molecule or a form of gp330 that lacks the cytoplasmic domain...

..The results also suggest that antibody-antigen complexes may be shed from the plasma membrane in both the glomerulus and the proximal tubule in this disease...

..Thus, cold preservation of tissues might impair, at least transiently, the polarized membrane expression and function of some transport proteins in renal epithelial cells...

..These results suggest that H(+)-ATPase is actively endocytosed and exocytosed in proton-secreting cells of the epididymis and vas deferens and that net proton secretion requires the participation of the v-SNARE cellubrevin...

..Our results indicate that although microtubules are involved in the accumulation of gp330-containing vesicles at the apical pole of the cell, other factors must be required for fusion with the plasma membrane to occur...

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..This relocation compensates for the absence of functional B1 and maintains the luminal pH in an acidic range that is compatible with fertility...

..The functional significance of the apparent species-dependent expression of AQP4 in proximal tubules is unknown, but may relate to physiological differences between rats and mice...

..This acidification mechanism is a potential target for novel strategies aimed at modulating the acidification capacity of parts of the male reproductive tract and, therefore, in regulating male fertility...

..These results provide direct evidence that a molecular water channel can spontaneously assemble in regular arrays...

..Thus, restoration of the defective endocytotic and processing function of PT epithelial cells might represent an effective strategy to limit urinary albumin loss, at least in some types of nephrotic syndrome...

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..In the present study, we further investigated AQP2 accumulation at the cell surface, and compared it with V2R (VP type 2 receptor) trafficking using cells that express epitope-tagged AQP2 and V2R...

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..In principal cells, the ATP6V0D1 isoform may have a physiological function that is distinct from its role in proton transport via the V-ATPase complex...

..This effect was inhibited by BAPTA-AM, demonstrating the participation of calcium in this process. This study, therefore, identifies BK as an important regulator of AQP9...

..The results show that the region of gp330 spanning amino acid residues 1114 to 1250 contains peptides capable of inducing pathogenic antibodies of Heymann nephritis without a contributory role of RAP...

..Tg transcytosis is a novel function of megalin, which usually transports ligands to lysosomes. Megalin-mediated transcytosis may regulate the extent of thyroid hormone release...

..This may have important implications on adaptational processes governing transcellular water flux and/or cell survival under extreme conditions of hypertonicity...

..This suggests that these enzymes have a close association and could be part of a protein complex that is involved in regulating renal distal proton secretion...

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..Therefore, modulation of the actin cortex by this severing and capping protein may represent a common mechanism by which these cells regulate their rate of proton secretion...

..These results demonstrate that differentiated subpopulations of proton-secreting epithelial cells appear early during epididymal development, and that the induction of H+ ATPase in these cells occurs prior to sexual maturation...

..We propose that the IMP clusters previously associated with vasopressin action represent sites of dynamin-dependent, clathrin-mediated endocytosis in which AQP2 is concentrated before internalization...

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..Elucidation of the mechanism(s) responsible for this phenotype will be of importance in understanding the origin and development of intercalated cells in the kidney...

..Thus mice lacking cPLA(2) develop an age-related defect in renal concentration that may be related to abnormal trafficking and/or folding of AQP1 in the proximal tubule, implicating cPLA(2) in these processes...

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..5 nm. These results provide a morphological signature for CHIP28 water channels and evidence for a tetrameric assembly of CHIP28 monomers in reconstituted proteoliposomes and cell membranes...

..The exclusive basolateral location of syntaxin 3 in situ, however, contrasts with the apical location of this SNARE protein in some kidney epithelial cells in culture...

..The results provide a framework on which to base and interpret future studies on the role of Arf GTPases in the multitude of cellular trafficking events that occur in renal tubular epithelial cells...

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..As sAC is expressed in other acid/base transporting epithelia, including kidney and choroid plexus, this cAMP-dependent signal transduction pathway may be a widespread mechanism that allows cells to sense and modulate extracellular pH...

..We conclude that direct stimulation of PKA activity by cAMP is necessary and sufficient for the alkaline pH-induced accumulation of V-ATPase in clear cell apical microvilli...

..In summary, these data suggest that the two presenilin 2 CTFs have different patterns of subcellular localization and that the N141I PS2 mutation alters the localization pattern of the PS2 caspase fragment...

..By analogy with kidney intercalated cells, these cell types may be specialized for acid secretion in the epididymis...

..This mechanism may play an important role in the pH-dependent regulation of receptor-mediated endocytosis in proximal tubules in situ...

..Unlike in rat, the mouse AE2c2 mRNA splice variant encoded a polypeptide with a novel predicted N-terminal amino acid sequence...

..The colocalization of NHE-RF and H(+)ATPase in B- but not A-intercalated cells suggests a role in generating, maintaining, or modulating the variable H(+)ATPase polarity that characterizes the B-cell phenotype...

..However, our results show no increase in cell surface V-ATPase activity in response to metabolic acidosis in ICs from these animals, consistent with their inability to appropriately acidify their urine under these conditions...

..Recent information about these pH-sensing mechanisms, which include the role of the V-ATPase itself as a pH sensor and the soluble adenylyl cyclase as a bicarbonate sensor, will be addressed in this review...

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..This degradative pathway may be an adaptive response to allow receptor-ligand association in the hypertonic and acidic environment of the renal medulla...

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..To summarize, we have identified the 70-kDa heat shock proteins as a AQP2 interactors and have shown for hsc70 that this interaction is involved in AQP2 trafficking...

..This suggests that calcitonin has a potential therapeutic use in nephrogenic diabetes insipidus...

..Fc is a potential new agent for the treatment of fibrosis and albuminuria in diabetic nephropathy and may reduce albuminuria by reducing TGF-beta1-induced disruptions of renal proximal tubule cell uptake of albumin...

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..AQPs may be involved not only in the transepithelial transport of water in the epididymis but also in the postnatal development of this organ, as suggested by the differential expression of AQP2...

..ClC-5 might facilitate endosome trafficking in the epididymis, as has been proposed in the kidney...

..The results of this dynamic epithelial surveillance can then be conveyed to the underlying cell populations of the lamina propria via these innate immune pattern recognition receptors...

..These results support the idea that, in addition to its role in reducing AQP2 endocytosis, VP increases AQP2 exocytosis...

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..However, this motif is not essential for the apical/basolateral sorting and polarized distribution of the V2R in LLC-PK1a cells or for adenylyl cyclase-mediated signal transduction...

..These findings suggest that V-ATPase may be involved in proton secretion in the OE and, as such, may be important for the pH homeostasis of the neuroepithelial mucous layer and/or for signal transduction in CO(2) detection...

..While the gradient is important for urinary concentration, it may also play a substantial role in fine-tuning of the vasopressin response through the V2R...

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..In conclusion, in the early stages of diabetic nephropathy, the PT plays a major role in the development of albuminuria, which may be preceded by peptideuria...

..These data indicate that the expression of AQP9, a likely candidate for apical transepithelial fluid and solute transport in several regions of the male reproductive tract, is modulated by androgens in the adult rat epididymis...

..Our aim was to characterize the developmental difference in cholera toxin (CT)-GM1-mediated endocytosis...

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..The potential role of S261 phosphorylation/dephosphorylation in vasopressin action remains to be determined...

..Here we discuss the design, use and advantages of the highly specific TGF-beta binding molecule, the soluble human TGF-beta receptor (sTbetaR.Fc) as a TGF-beta sequestering agent...

..These findings indicate that in addition to its role in the acidification of intracellular organelles, the B2 isoform could also contribute to transepithelial proton secretion and the maintenance of acid-base homeostasis...

..Thus, these data support the hypothesis that these RGS proteins sequester coatomer in the cytoplasm and inhibit its recruitment onto Golgi membranes, which may in turn modulate Golgi-plasma membrane or intra-Golgi transport...

..We propose that CFTR is an important regulator of AQP9 and that the interaction between AQP9, NHERF1, and CFTR may facilitate the activation of AQP9 by cAMP...

..Our results underscore the multiorgan role of caveolae in metabolic regulation and the obligate presence of Cavin for caveolae formation...

..The differential localization of two very similar integral membrane proteins suggests that mechanisms other than size-dependent exclusion regulate their passage to the inner nuclear membrane...

..These proteomic databases provide a framework for comprehensive future analysis of the common and distinct functions of V-ATPase-B1-expressing cells in the kidney and epididymis...

..These events may underlie the loss of podocyte barrier function in membranous nephropathy...

..Treatment with omacetaxine decreased the number of leukemia stem cells and prolonged the survival of mice with BCR-ABL-induced CML or B-ALL...

..These results suggest that down-regulation of the Ke 6 gene may lead to elevated corticosterone levels, mediated through an inhibition of 11betaHSD-1 activity...

..The observations indicate high level expression of adseverin in specific cells of the kidney and colon, and suggest a previously unrecognized function of adseverin in epithelial cell function...

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..Since RAP is found largely within cells, its major physiological function may be concerned with intracellular assembly or trafficking of the receptors to which it binds...

..Our data show that expression of AQP9 in the developing rat epididymis is downregulated by neonatal DES, GNRHa, EE, and flutamide, and that the effects mediated by estrogens can be prevented by testosterone administration...

..Modulation of the V-ATPase-rich cell phenotype and the pathophysiology of the V-ATPase in humans and experimental animals are also discussed...

..5 days. In adolescent females, duration of HPV 16 detection was significantly longer when TSN-PCR-16 was combined with LA-HPV. Some apparently cleared HPV 16 could be shown to persist at low levels using nested PCR...

..We assessed the effects of these drug combinations on progression of chronic kidney disease...

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..Two of the TRPC6 mutants had increased current amplitudes. These data show that TRPC6 channel activity at the slit diaphragm is essential for proper regulation of podocyte structure and function...

..Taken together, these results suggest that Dragon may enhance BMP signaling in renal tubular epithelial cells and maintain normal renal physiology...

..The present article reviews our current knowledge regarding the distribution and function of aquaporins in the male excurrent duct...

..We propose a paradigm in which basal cells scan and sense the luminal environment of pseudostratified epithelia and modulate epithelial function by a mechanism involving crosstalk with other epithelial cells...

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..This study demonstrates that Drosophila provides a viable model system in which to dissect the complex interactions that regulate phagocytosis...

..The results have implications for medical and biotechnology applications of SERS nanosensors in cells...

..The effects of microtubule disruption by colchicine on NHE3 trafficking in PT and the potential role of NHERF in this process have not been studied...

..Providing laser microdissection access and expertise to the MGH research community will be an important part of our mission and bridges the gap between pure microscopy studies and functional genomics that take advantage ..

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..Thus, a wide-range of projects and investigators will benefit from this equipment, which will be integrated into a Core facility that has been operational for over 15 years. ..

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..An important and unique aspect of the proposed studies is that they will mostly be carried out in situ using markers of endogenous proteins that are of functional importance in kidney physiology...