Role of microvillar cell surfaces in the regulation of  glucose uptake and organization of energy metabolism

Lange, Klaus

doi:10.1152/ajpcell.2002.282.1.c1

Cited by 56 publications

(27 citation statements)

References 196 publications

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“…As shown in the graph, there is a clear increase in the glucose uptake for the cells subjected to high media flow (blue/white points) with a maximum of~95% glucose uptake 6 h after the FSS, compared to the more stable glucose uptake (between~75 and~80%) for the control experiment (red/white points). Increased glucose uptake may be related to the expression of multiple transporter types and/or better efficiency of the glucose uptake receptors in the microvilli 53 , and would be consistent with an increased adsorption of nutrients allowed by higher surface area at the apical surface.…”

Section: Results and Discussion Flow Shear Stress Mechanical Stimulationmentioning

confidence: 90%

Organic transistor platform with integrated microfluidics for in-line multi-parametric in vitro cell monitoring

et al. 2017

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Future drug discovery and toxicology testing could benefit significantly from more predictive and multi-parametric readouts from in vitro models. Despite the recent advances in the field of microfluidics, and more recently organ-on-a-chip technology, there is still a high demand for real-time monitoring systems that can be readily embedded with microfluidics. In addition, multi-parametric monitoring is essential to improve the predictive quality of the data used to inform clinical studies that follow. Here we present a microfluidic platform integrated with in-line electronic sensors based on the organic electrochemical transistor. Our goals are twofold, first to generate a platform to host cells in a more physiologically relevant environment (using physiologically relevant fluid shear stress (FSS)) and second to show efficient integration of multiple different methods for assessing cell morphology, differentiation, and integrity. These include optical imaging, impedance monitoring, metabolite sensing, and a wound-healing assay. We illustrate the versatility of this multi-parametric monitoring in giving us increased confidence to validate the improved differentiation of cells toward a physiological profile under FSS, thus yielding more accurate data when used to assess the effect of drugs or toxins. Overall, this platform will enable high-content screening for in vitro drug discovery and toxicology testing and bridges the existing gap in the integration of in-line sensors in microfluidic devices.

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Section: Results and Discussion Flow Shear Stress Mechanical Stimulationmentioning

confidence: 90%

Organic transistor platform with integrated microfluidics for in-line multi-parametric in vitro cell monitoring

et al. 2017

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“…Do actin filament bundles have an active role in microvillus growth, or are they passively filling the stem of the growing microvillus, as described previously for another type of membrane protrusion (46)? Microvillus-type cell protrusions represent a distinct cellular compartment that harbors important regulatory functions (43). Among others, multidrug resistance transporter proteins (51,52) and ErbB2 receptors (53) reside in microvilli.…”

Section: Discussionmentioning

confidence: 99%

Hyaluronan Synthesis Induces Microvillus-like Cell Surface Protrusions

Kultti

Rilla

Tiihonen

et al. 2006

Journal of Biological Chemistry

124

134

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Hyaluronan synthases (HASs) are plasma membrane enzymes that simultaneously elongate, bind, and extrude the growing hyaluronan chain directly into extracellular space. In cells transfected with green fluorescent protein (GFP)-tagged Has3, the dorsal surface was decorated by up to 150 slender, 3-20-m-long microvillus-type plasma membrane protrusions, which also contained filamentous actin, the hyaluronan receptor CD44, and lipid raft microdomains. Enzymatic activity of HAS was required for the growth of the microvilli, which were not present in cells transfected with other GFP proteins or inactive GFP-Has3 mutants or in cells incubated with exogenous soluble hyaluronan. The microvilli induced by HAS3 were gradually withered by introduction of an inhibitor of hyaluronan synthesis and rapidly retracted by hyaluronidase digestion, whereas they were not affected by competition with hyaluronan oligosaccharides and disruption of the CD44 gene, suggesting independence of hyaluronan receptors. The data bring out the novel concept that the glycocalyx created by dense arrays of hyaluronan chains, tethered to HAS during biosynthesis, can induce and maintain prominent microvilli.Vertebrate cells display slender plasma membrane protrusions like filopodia, microspikes, and microvilli, the formation and maintenance of which are thought to depend on the dynamics of a bundle of actin filaments in the core of these extensions (1). In selected environments, most of the components in the actin polymerization apparatus, when overexpressed or experimentally activated, have been reported to increase the growth of filopodia or microvilli (2-7). This suggests that there is a strong intrinsic potential in cells to display these extensions, ready for implementation by factors even outside the effector and signaling chains directly related to actin. Indeed, at the molecular level, mechanisms that induce the growth of microvilli in vivo are still somewhat obscure (8). We present a novel factor, active hyaluronan synthesis, apparently unrelated to any of the previously described signaling or actin polymerization processes, that triggers extensive microvillus formation in several cell types. Interestingly, the process is primarily driven by the cell surface glycocalyx rather than intracellular systems.Hyaluronan is an ubiquitous pericellular and extracellular matrix glycosaminoglycan important in embryonic development (9), wound healing (10), inflammation (11, 12), mammalian fertilization (13), and cancer (14). It is involved in cell adhesion (15), migration (16 -19), proliferation and epithelial-mesenchymal transition (9), resistance to apoptosis, and multidrug resistance (14). Some of its effects are thought to be mediated by an ability to form a hydrated pericellular matrix, a coat that can modify cellular interactions with other matrix components and neighboring cells, directly regulating processes such as differentiation and migration (20). Some of the biological signals elicited by hyaluronan are dependent on its CD44 receptor on cell su...

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“…It has been reported that some molecules such as epidermal growth factor, human insulin receptor, glucagon receptor, and certain adhesion molecules or ion channels have a preferential initial localization in microvillus-like protrusions (6,8,13,14).…”

Section: Downloaded Frommentioning

confidence: 99%

“…On the other hand, the microvillus-like protrusions are highly enriched in actin-binding proteins (13,17), which probably provide driving forces for the polarization of molecules in local membranes.…”

Section: Downloaded Frommentioning

confidence: 99%

Fluorescence-topographic NSOM directly visualizes peak-valley polarities of GM1/GM3 rafts in cell membrane fluctuations

Chen

Qin

Chen

2008

Journal of Lipid Research

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Simultaneous fluorescence-topographic nanoscale imaging of cell-surface molecules in the context of membrane ultra-structures has not been reported. Here, near-field scanning optical microscopy (NSOM)-based direct fluorescence-topographic imaging indicated that GM3 rafts/ nanodomains (190.0 6 49.8 nm ranging 84.5-365.0 nm) were localized predominantly on the peaks of microvillus-like protrusions in the apical membrane of GM3 1 Madin-Darby canine kidney cells, whereas GM1 rafts/nanodomains (159.5 6 63.8 nm ranging 42-360 nm) were distributed mainly on the slops of protrusions or the valleys between protrusions in the plasma membranes of GM1 1 MDCK cells. The data demonstrated that gangliosides polarized not only in a well-known apical-basolateral manner but also in the more microscopic peak-valley manner, implicating unique distribution of GM1 or GM3 in cell-surface fluctuations on the apical membrane of polarized cells. The peak-valley polarities of gangliosides also implicated their different functions relevant to lipid rafts, microvilli, or cellular processes. Importantly, our study demonstrated for the first time that the NSOM-based direct fluorescence-topographic imaging is unique and powerful for elucidating nanoscale distribution of specific cellsurface molecules in membrane fluctuations.-Chen, Y., J. Qin, and Z. W. Chen. Fluorescence-topographic NSOM directly visualizes peak-valley polarities of GM1/GM3 rafts in cell membrane fluctuations. J. Lipid Res. 2008Res. . 49: 2268Res. -2275 Supplementary key words near-field scanning optical microscopyMorphological, chemical, and functional polarities of membrane lipids (1) are well described and are relevant to lipid raft formation and cellular signaling. While different lipid components, especially glycolipids, are distributed in the apical-basolateral manner in the plasma membranes of epithelial cells (2), the ganglioside-enriched rafts on T lymphocytes can redistribute asymmetrically in a leadingedge-uropod manner upon cell activation (3). Despite identification of apical-basolateral and leading-edge-uropod distributions of membrane lipids, little is known about nanostructures and precise topographic localization of gangliosides or lipid rafts in the context of biological membrane ultrastructures, such as microvilli or protrusions/valleys.Widely used conventional imaging techniques have a limited capability to elucidate fluorescence-topographic distribution of cell-surface molecules at nanoscale. The traditional fluorescence instruments including confocal microscopy do not have enough optical resolution for detection of nanscale ganglioside clusters. Fluorescence resonance energy transfer measurement or single particle tracking technique is unable to reveal the nanoscale topographic localization of molecules on membrane surface. Rapidly developed atomic force microscopy fails to detect fluorescence information. The high-resolution electron microscopy (EM) is often limited by uncertain fidelity or reliability due to the complicated sample-preparing ...

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Role of microvillar cell surfaces in the regulation of glucose uptake and organization of energy metabolism

Cited by 56 publications

References 196 publications

Organic transistor platform with integrated microfluidics for in-line multi-parametric in vitro cell monitoring

Organic transistor platform with integrated microfluidics for in-line multi-parametric in vitro cell monitoring

Hyaluronan Synthesis Induces Microvillus-like Cell Surface Protrusions

Fluorescence-topographic NSOM directly visualizes peak-valley polarities of GM1/GM3 rafts in cell membrane fluctuations

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