Sadtler, Sven ; Laube, Bodo ; Lashub, Alhassan ; Nicke, Annette ; Betz, Heinrich ; Schmalzing, Günther (2003)
A basic cluster determines topology of the cytoplasmic M3-M4 loop of the glycine receptor alpha1 subunit.
In: The Journal of biological chemistry, 278 (19)
Artikel, Bibliographie
Kurzbeschreibung (Abstract)
The inhibitory glycine receptor is a member of the ligand-gated ion channel superfamily of neurotransmitter receptors, which are composed of homologous subunits with four transmembrane segments (M1-M4), each. Here, we demonstrate that the correct topology of the glycine receptor alpha1 subunit depends critically on six positively charged residues within a basic cluster, RFRRKRR, located in the large cytoplasmic loop (designated M3-M4 loop) following the C-terminal end of M3. Neutralization of one or more charges of this cluster, but not of other charged residues in the M3-M4 loop, led to an aberrant translocation into the endoplasmic reticulum lumen of the M3-M4 loop. However, when two of the three basic charges located in the ectodomain linking M2 and M3 were neutralized, in addition to two charges of the basic cluster, endoplasmic reticulum disposition of the M3-M4 loop was prevented. We conclude that a high density of basic residues C-terminal to M3 is required to compensate for the presence of positively charged residues in the M2-M3 ectodomain, which otherwise impair correct membrane integration of the M3 segment.
| Typ des Eintrags: | Artikel |
|---|---|
| Erschienen: | 2003 |
| Autor(en): | Sadtler, Sven ; Laube, Bodo ; Lashub, Alhassan ; Nicke, Annette ; Betz, Heinrich ; Schmalzing, Günther |
| Art des Eintrags: | Bibliographie |
| Titel: | A basic cluster determines topology of the cytoplasmic M3-M4 loop of the glycine receptor alpha1 subunit. |
| Sprache: | Englisch |
| Publikationsjahr: | 2003 |
| Titel der Zeitschrift, Zeitung oder Schriftenreihe: | The Journal of biological chemistry |
| Jahrgang/Volume einer Zeitschrift: | 278 |
| (Heft-)Nummer: | 19 |
| Kurzbeschreibung (Abstract): | The inhibitory glycine receptor is a member of the ligand-gated ion channel superfamily of neurotransmitter receptors, which are composed of homologous subunits with four transmembrane segments (M1-M4), each. Here, we demonstrate that the correct topology of the glycine receptor alpha1 subunit depends critically on six positively charged residues within a basic cluster, RFRRKRR, located in the large cytoplasmic loop (designated M3-M4 loop) following the C-terminal end of M3. Neutralization of one or more charges of this cluster, but not of other charged residues in the M3-M4 loop, led to an aberrant translocation into the endoplasmic reticulum lumen of the M3-M4 loop. However, when two of the three basic charges located in the ectodomain linking M2 and M3 were neutralized, in addition to two charges of the basic cluster, endoplasmic reticulum disposition of the M3-M4 loop was prevented. We conclude that a high density of basic residues C-terminal to M3 is required to compensate for the presence of positively charged residues in the M2-M3 ectodomain, which otherwise impair correct membrane integration of the M3 segment. |
| Fachbereich(e)/-gebiet(e): | 10 Fachbereich Biologie 10 Fachbereich Biologie > Neurophysiologie und neurosensorische Systeme ?? fb10_zoologie ?? |
| Hinterlegungsdatum: | 11 Apr 2011 09:45 |
| Letzte Änderung: | 05 Mär 2019 06:48 |
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