@article{AtakLanglhoferSchaeferetal.2015,
  author    = {Atak, Sinem and Langlhofer, Georg and Schaefer, Natascha and Kessler, Denise and Meiselbach, Heike and Delto, Carolyn and Schindelin, Hermann and Villmann, Carmen},
  title     = {Disturbances of ligand potency and enhanced degradation of the human glycine receptor at affected positions G160 and T162 originally identified in patients suffering from hyperekplexia},
  series = {Frontiers in Molecular Neuroscience},
  volume    = {8},
  journal   = {Frontiers in Molecular Neuroscience},
  number    = {79},
  doi       = {10.3389/fnmol.2015.00079},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-144818},
  year      = {2015},
  abstract  = {Ligand-binding of Cys-loop receptors is determined by N-terminal extracellular loop structures from the plus as well as from the minus side of two adjacent subunits in the pentameric receptor complex. An aromatic residue in loop B of the glycine receptor (GIyR) undergoes direct interaction with the incoming ligand via a cation-π interaction. Recently, we showed that mutated residues in loop B identified from human patients suffering from hyperekplexia disturb ligand-binding. Here, we exchanged the affected human residues by amino acids found in related members of the Cys-loop receptor family to determine the effects of side chain volume for ion channel properties. GIyR variants were characterized in vitro following transfection into cell lines in order to analyze protein expression, trafficking, degradation and ion channel function. GIyR α1 G160 mutations significantly decrease glycine potency arguing for a positional effect on neighboring aromatic residues and consequently glycine-binding within the ligand-binding pocket. Disturbed glycinergic inhibition due to T162 α1 mutations is an additive effect of affected biogenesis and structural changes within the ligand-binding site. Protein trafficking from the ER toward the ER-Golgi intermediate compartment, the secretory Golgi pathways and finally the cell surface is largely diminished, but still sufficient to deliver ion channels that are functional at least at high glycine concentrations. The majority of T162 mutant protein accumulates in the ER and is delivered to ER-associated proteasomal degradation. Hence, G160 is an important determinant during glycine binding. In contrast, 1162 affects primarily receptor biogenesis whereas exchanges in functionality are secondary effects thereof.},
  language  = {en}
}
@article{ScholzGehringGuanetal.2015,
  author    = {Scholz, Nicole and Gehring, Jennifer and Guan, Chonglin and Ljaschenko, Dmitrij and Fischer, Robin and Lakshmanan, Vetrivel and Kittel, Robert J. and Langenhan, Tobias},
  title     = {The adhesion GPCR Latrophilin/CIRL shapes mechanosensation},
  series = {Cell Reports},
  volume    = {11},
  journal   = {Cell Reports},
  doi       = {10.1016/j.celrep.2015.04.008},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-148626},
  pages     = {866-874},
  year      = {2015},
  abstract  = {G-protein-coupled receptors (GPCRs) are typically regarded as chemosensors that control cellular states in response to soluble extracellular cues. However, the modality of stimuli recognized through adhesion GPCR (aGPCR), the second largest class of the GPCR superfamily, is unresolved. Our study characterizes the Drosophila aGPCR Latrophilin/dCirl, a prototype member of this enigmatic receptor class. We show that dCirl shapes the perception of tactile, proprioceptive, and auditory stimuli through chordotonal neurons, the principal mechanosensors of Drosophila. dCirl sensitizes these neurons for the detection of mechanical stimulation by amplifying their input-output function. Our results indicate that aGPCR may generally process and modulate the perception of mechanical signals, linking these important stimuli to the sensory canon of the GPCR superfamily.},
  language  = {en}
}
@article{WilleSchuemannWreeetal.2015,
  author    = {Wille, Michael and Sch{\"u}mann, Antje and Wree, Andreas and Kreutzer, Michael and Glocker, Michael O. and Mutzbauer, Grit and Schmitt, Oliver},
  title     = {The Proteome Profiles of the Cerebellum of Juvenile, Adult and Aged Rats-An Ontogenetic Study},
  series = {International Journal of Molecular Sciences},
  volume    = {16},
  journal   = {International Journal of Molecular Sciences},
  doi       = {10.3390/ijms160921454},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-151347},
  pages     = {21454 -- 21485},
  year      = {2015},
  abstract  = {In this study, we searched for proteins that change their expression in the cerebellum (Ce) of rats during ontogenesis. This study focuses on the question of whether specific proteins exist which are differentially expressed with regard to postnatal stages of development. A better characterization of the microenvironment and its development may result from these study findings. A differential two-dimensional polyacrylamide gel electrophoresis (2DE) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) analysis of the samples revealed that the number of proteins of the functional classes differed depending on the developmental stages. Especially members of the functional classes of biosynthesis, regulatory proteins, chaperones and structural proteins show the highest differential expression within the analyzed stages of development. Therefore, members of these functional protein groups seem to be involved in the development and differentiation of the Ce within the analyzed development stages. In this study, changes in the expression of proteins in the Ce at different postnatal developmental stages (postnatal days (P) 7, 90, and 637) could be observed. At the same time, an identification of proteins which are involved in cell migration and differentiation was possible. Especially proteins involved in processes of the biosynthesis and regulation, the dynamic organization of the cytoskeleton as well as chaperones showed a high amount of differentially expressed proteins between the analyzed dates.},
  language  = {en}
}