ORCID Profile
0000-0003-1862-7357
Current Organisation
University of Würzburg
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Publisher: The Endocrine Society
Date: 2015
DOI: 10.1210/ME.2014-1173
Publisher: Elsevier BV
Date: 03-2016
Publisher: Proceedings of the National Academy of Sciences
Date: 06-05-2013
Publisher: Elsevier BV
Date: 02-2016
DOI: 10.1016/J.MCE.2015.12.007
Abstract: Mature TGF-β proteins are used in vivo to promote bone growth, combat obesity, reverse fibrosis and pulmonary arterial hypertension, and as potential rejuvenation factors. However, the serum half-life of this family of growth factors is short (∼5 min), limiting their therapeutic potential. Because TGF-β proteins are normally secreted from cells with their prodomains attached, we considered whether these molecules could extend the in vivo half-life and activity of their respective growth factors. Using activin A as a model ligand, we initially modified the cleavage site between the pro- and mature domains to ensure complete processing of the activin A precursor. Co-immunoprecipitation studies confirmed mature activin A is secreted from cells in a non-covalent complex with its prodomain, however, the affinity of this interaction is not sufficient to suppress activin A in vitro biological activity. The plasma clearance profiles of purified pro- and mature activin A were determined over a 4 h period in adult male rats. Both activin forms demonstrated a two-phase decay, with the half-life of pro-activin A (t1/2 fast = 12.5 min, slow = 31.0 min) being greater than that of mature activin A (t1/2 fast = 5.5 min, slow = 20.3 min). Both pro- and mature activin A induced significant increases in serum follicle stimulating hormone levels after 4 h, but no differences were observed in the relative in vivo bioactivities of the two activin isoforms. Increased serum half-life of activin A in the presence of its prodomain identifies a new means to increase the therapeutic effectiveness of TGF-β proteins.
Publisher: Cold Spring Harbor Laboratory
Date: 22-09-2021
DOI: 10.1101/2021.09.21.461191
Abstract: As the major sugar-producing crop in the northern hemisphere, sugar beet taproots store sucrose at a concentration of about 20 %. While the vacuolar sucrose loader TST has already been identified in the taproot, sugar transporters mediating sucrose uptake across the plasma membrane of taproot parenchyma cells remained unknown. We electrophysiologically examined taproots for proton-coupled sugar uptake and identified potentially involved transporters by transcriptomic profiling. After cloning, the transporter features were studied in the heterologous Xenopus laevis oocyte expression system using the two-electrode voltage cl technique. Insights into the structure were gained by 3D homology modeling. As with glucose, sucrose stimulation of taproot parenchyma cells caused inward H + -fluxes and plasma membrane depolarization, indicating a sugar roton symport mechanism. As one potential candidate for sugar uploading, the BvPMT5a was characterized as a H + -driven low-affinity glucose transporter, which does not transport sucrose. BvSTP13 operated as a high-affinity H + /sugar symporter, transporting glucose and to some extent sucrose due to a binding cleft plasticity. Both transporter genes were upregulated upon cold exposure, with the transport capacity of BvSTP13 being more cold-resistant than BvPMT5a. Identification of BvPMT5a and BvSTP13 as taproot sugar transporters could improve breeding of cold-tolerant sugar beet to provide a sustainable energy crop.
Publisher: Elsevier BV
Date: 02-2016
Publisher: Elsevier BV
Date: 09-2015
Location: United States of America
Location: Germany
No related grants have been discovered for Thomas Mueller.