at Google ScholarTitle data
Schäfer, Natascha ; Kluck, Christoph J. ; Price, Kerry L. ; Meiselbach, Heike ; Vornberger, Nadine ; Schwarzinger, Stephan ; Hartmann, Stephanie ; Langlhofer, Georg ; Schulz, Solveig ; Schlegel, Nadja ; Brockmann, Knut ; Lynch, Bryan ; Becker, Cord-Michael ; Lummis, Sarah C. R. ; Villmann, Carmen:
Disturbed Neuronal ER-Golgi Sorting of Unassembled Glycine Receptors Suggests Altered Subcellular Processing Is a Cause of Human Hyperekplexia.
In: The Journal of Neuroscience.
Vol. 35
(2015)
Issue 1
.
- pp. 422-437.
ISSN 1529-2401
DOI: https://doi.org/10.1523/JNEUROSCI.1509-14.2015
Abstract in another language
Recent studies on the pathogenic mechanisms of recessive hyperekplexia indicate disturbances in glycine receptor (GlyR) α1 biogenesis. Here, we examine the properties of a range of novel glycine receptor mutants identified in human hyperekplexia patients using expression in transfected cell lines and primary neurons. All of the novel mutants localized in the large extracellular domain of the GlyR α1 have reduced cell surface expression with a high proportion of receptors being retained in the ER, although there is forward trafficking of glycosylated subpopulations into the ER-Golgi intermediate compartment and cis-Golgi compartment. CD spectroscopy revealed that the mutant receptors have proportions of secondary structural elements similar to wild-type receptors. Two mutants in loop B (G160R, T162M) were functional, but none of those in loop D/β2-3 were. One nonfunctional truncated mutant (R316X) could be rescued by coexpression with the lacking C-terminal domain. We conclude that a proportion of GlyR α1 mutants can be transported to the plasma membrane but do not necessarily form functional ion channels. We suggest that loop D/β2-3 is an important determinant for GlyR trafficking and functionality, whereas alterations to loop B alter agonist potencies, indicating that residues here are critical elements in ligand binding.
Further data
| Item Type: | Article in a journal |
|---|---|
| Refereed: | Yes |
| Institutions of the University: | Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry > Former Professors > Chair Biopolymers - Univ.-Prof. Dr. Paul Rösch Faculties Faculties > Faculty of Biology, Chemistry and Earth Sciences Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry > Former Professors Faculties > Faculty of Biology, Chemistry and Earth Sciences > Department of Chemistry > Chair Biochemistry IV - Biophysical Chemistry Research Institutions > Central research institutes > Nordbayerisches Zentrum für NMR-Spektroskopie - NMR-Zentrum |
| Result of work at the UBT: | Yes |
| DDC Subjects: | 500 Science > 540 Chemistry 500 Science > 570 Life sciences, biology |
| Date Deposited: | 30 Jan 2019 11:02 |
| Last Modified: | 26 Sep 2024 07:31 |
| URI: | https://eref.uni-bayreuth.de/id/eprint/47134 |