The Experts below are selected from a list of 183 Experts worldwide ranked by ideXlab platform

Thomas Weidemann - One of the best experts on this subject based on the ideXlab platform.

  • Diffusion of Single-Pass Transmembrane Receptors: From the Plasma Membrane into Giant Liposomes
    The Journal of Membrane Biology, 2017
    Co-Authors: Remigiusz Worch, Zdenek Petrášek, Petra Schwille, Thomas Weidemann
    Abstract:

    To quantitatively examine the effect of membrane organization on lateral diffusion, we studied fluorescent carbocyanine lipid analogues and EGFP-tagged, Single-Pass Transmembrane Proteins in systems of decreasing complexity: (i) the plasma membrane (PM) of living cells, (ii) paraformaldehyde/dithiothreitol-induced giant plasma membrane vesicles (GPMVs), and (iii) giant unilamellar vesicles (GUVs) under physiological buffer conditions. A truncated, signaling-deficient interleukin-4 receptor subunit, showing efficient accumulation in the plasma membrane, served as a model Transmembrane protein. Two-dimensional diffusion coefficients ( D ) were determined by fluorescence correlation spectroscopy (FCS) either at fixed positions (single-point, spFCS) or while scanning a circular orbit (circular scanning, csFCS). Consistent with a different inclusion sizes in the membrane, lipids diffuse slightly faster than the single-spanning membrane Proteins in both membrane systems, GUVs and GPMVs. In GPMVs lipids and Proteins consistently experienced a fivefold larger viscosity than in GUVs, reflecting the significant fraction of plasma membrane-derived Proteins partitioning into GPMVs. Lipid and protein diffusion in the PM was, respectively, 2 times and 4–5 times slower in comparison to GPMVs. This discrepancy was quantitatively confirmed by csFCS. The similarity of diffusion of receptors and lipids in GPMVs and GUVs and its significant difference in the plasma membrane suggest that protein domains as small as EGFP convey sensitivity to the actin cortex on various length scales.

  • Agonist mobility on supported lipid bilayers affects Fas mediated death response
    FEBS Letters, 2015
    Co-Authors: M. Florencia Sánchez, Valeria Levi, Thomas Weidemann, Dolores C. Carrer
    Abstract:

    Extrinsic apoptosis is initiated by recognition and clustering of the Single-Pass Transmembrane Proteins Fas ligand and Fas expressed at the surface of closely apposed lymphocytes and target cells, respectively. Since Fas-mediated death response was mainly studied with soluble antibodies, the mobility constraints for receptor activation by a membrane embedded agonist is not well understood. We explored this influence by stimulating apoptosis on functionalized supported lipid bilayers, where we quantified agonist mobility by z-scan fluorescence correlation spectroscopy. Using different lipid compositions, we show that the apoptotic response correlates with increased lateral mobility of the agonist in the lipid bilayer.

Makoto Kuroo - One of the best experts on this subject based on the ideXlab platform.

  • tissue specific expression of βklotho and fibroblast growth factor fgf receptor isoforms determines metabolic activity of fgf19 and fgf21
    Journal of Biological Chemistry, 2007
    Co-Authors: Hiroshi Kurosu, Mihwa Choi, Addie S Dickson, Anna V Eliseenkova, Steven A Kliewer, Yasushi Ogawa, Moosa Mohammadi, Regina Goetz, Kevin P Rosenblatt, Makoto Kuroo
    Abstract:

    The fibroblast growth factor (FGF) 19 subfamily of ligands, FGF19, FGF21, and FGF23, function as hormones that regulate bile acid, fatty acid, glucose, and phosphate metabolism in target organs through activating FGF receptors (FGFR1–4). We demonstrated that Klotho and βKlotho, homologous Single-Pass Transmembrane Proteins that bind to FGFRs, are required for metabolic activity of FGF23 and FGF21, respectively. Here we show that, like FGF21, FGF19 also requires βKlotho. Both FGF19 and FGF21 can signal through FGFR1–3 bound by βKlotho and increase glucose uptake in adipocytes expressing FGFR1. Additionally, both FGF19 and FGF21 bind to the βKlotho-FGFR4 complex; however, only FGF19 signals efficiently through FGFR4. Accordingly, FGF19, but not FGF21, activates FGF signaling in hepatocytes that primarily express FGFR4 and reduces transcription of CYP7A1 that encodes the rate-limiting enzyme for bile acid synthesis. We conclude that the expression of βKlotho, in combination with particularFGFR isoforms, determines the tissue-specific metabolic activities of FGF19 and FGF21.

Jinlong Chen - One of the best experts on this subject based on the ideXlab platform.

  • c terminal tail of fgf19 determines its specificity toward klotho co receptors
    Journal of Biological Chemistry, 2008
    Co-Authors: Xinle Wu, Jennifer Weiszmann, Jamila Gupte, Jennitte Stevens, Wenyan Shen, Bryan Lemon, Richard A Lindberg, Xiaofan Li, Nessa Hawkins, Jinlong Chen
    Abstract:

    FGF19 subfamily Proteins (FGF19, FGF21, and FGF23) are unique members of fibroblast growth factors (FGFs) that regulate energy, bile acid, glucose, lipid, phosphate, and vitamin D homeostasis in an endocrine fashion. Their activities require the presence of α or βKlotho, two related Single-Pass Transmembrane Proteins, as co-receptors in relevant target tissues. We previously showed that FGF19 can bind to both α and βKlotho, whereas FGF21 and FGF23 can bind only to either βKlotho or αKlotho, respectively in vitro. To determine the mechanism regulating the binding and specificity among FGF19 subfamily members to Klotho family Proteins, chimeric Proteins between FGF19 subfamily members or chimeric Proteins between Klotho family members were constructed to probe the interaction between those two families. Our results showed that a chimera of FGF19 with the FGF21 C-terminal tail interacts only with βKlotho and a chimera with the FGF23 C-terminal tail interacts only with αKlotho. FGF signaling assays also reflected the change of specificity we observed for the chimeras. These results identified the C-terminal tail of FGF19 as a region necessary for its recognition of Klotho family Proteins. In addition, chimeras between α and βKlotho were also generated to probe the regions in Klotho Proteins that are important for signaling by this FGF subfamily. Both FGF23 and FGF21 require intact α or βKlotho for signaling, respectively, whereas FGF19 can signal through a Klotho chimera consisting of the N terminus of αKlotho and the C terminus of βKlotho. Our results provide the first glimpse of the regions that regulate the binding specificity between this unique family of FGFs and their co-receptors.

Remigiusz Worch - One of the best experts on this subject based on the ideXlab platform.

  • Diffusion of Single-Pass Transmembrane Receptors: From the Plasma Membrane into Giant Liposomes
    The Journal of Membrane Biology, 2017
    Co-Authors: Remigiusz Worch, Zdenek Petrášek, Petra Schwille, Thomas Weidemann
    Abstract:

    To quantitatively examine the effect of membrane organization on lateral diffusion, we studied fluorescent carbocyanine lipid analogues and EGFP-tagged, Single-Pass Transmembrane Proteins in systems of decreasing complexity: (i) the plasma membrane (PM) of living cells, (ii) paraformaldehyde/dithiothreitol-induced giant plasma membrane vesicles (GPMVs), and (iii) giant unilamellar vesicles (GUVs) under physiological buffer conditions. A truncated, signaling-deficient interleukin-4 receptor subunit, showing efficient accumulation in the plasma membrane, served as a model Transmembrane protein. Two-dimensional diffusion coefficients ( D ) were determined by fluorescence correlation spectroscopy (FCS) either at fixed positions (single-point, spFCS) or while scanning a circular orbit (circular scanning, csFCS). Consistent with a different inclusion sizes in the membrane, lipids diffuse slightly faster than the single-spanning membrane Proteins in both membrane systems, GUVs and GPMVs. In GPMVs lipids and Proteins consistently experienced a fivefold larger viscosity than in GUVs, reflecting the significant fraction of plasma membrane-derived Proteins partitioning into GPMVs. Lipid and protein diffusion in the PM was, respectively, 2 times and 4–5 times slower in comparison to GPMVs. This discrepancy was quantitatively confirmed by csFCS. The similarity of diffusion of receptors and lipids in GPMVs and GUVs and its significant difference in the plasma membrane suggest that protein domains as small as EGFP convey sensitivity to the actin cortex on various length scales.

Hiroshi Kurosu - One of the best experts on this subject based on the ideXlab platform.

  • tissue specific expression of βklotho and fibroblast growth factor fgf receptor isoforms determines metabolic activity of fgf19 and fgf21
    Journal of Biological Chemistry, 2007
    Co-Authors: Hiroshi Kurosu, Mihwa Choi, Addie S Dickson, Anna V Eliseenkova, Steven A Kliewer, Yasushi Ogawa, Moosa Mohammadi, Regina Goetz, Kevin P Rosenblatt, Makoto Kuroo
    Abstract:

    The fibroblast growth factor (FGF) 19 subfamily of ligands, FGF19, FGF21, and FGF23, function as hormones that regulate bile acid, fatty acid, glucose, and phosphate metabolism in target organs through activating FGF receptors (FGFR1–4). We demonstrated that Klotho and βKlotho, homologous Single-Pass Transmembrane Proteins that bind to FGFRs, are required for metabolic activity of FGF23 and FGF21, respectively. Here we show that, like FGF21, FGF19 also requires βKlotho. Both FGF19 and FGF21 can signal through FGFR1–3 bound by βKlotho and increase glucose uptake in adipocytes expressing FGFR1. Additionally, both FGF19 and FGF21 bind to the βKlotho-FGFR4 complex; however, only FGF19 signals efficiently through FGFR4. Accordingly, FGF19, but not FGF21, activates FGF signaling in hepatocytes that primarily express FGFR4 and reduces transcription of CYP7A1 that encodes the rate-limiting enzyme for bile acid synthesis. We conclude that the expression of βKlotho, in combination with particularFGFR isoforms, determines the tissue-specific metabolic activities of FGF19 and FGF21.