TU Darmstadt / ULB / TUbiblio

A basic cluster determines topology of the cytoplasmic M3-M4 loop of the glycine receptor alpha1 subunit.

Sadtler, Sven and Laube, Bodo and Lashub, Alhassan and Nicke, Annette and Betz, Heinrich and 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, pp. 16782-90, 278, (19), ISSN 0021-9258, [Article]

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.

Item Type: Article
Erschienen: 2003
Creators: Sadtler, Sven and Laube, Bodo and Lashub, Alhassan and Nicke, Annette and Betz, Heinrich and Schmalzing, Günther
Title: A basic cluster determines topology of the cytoplasmic M3-M4 loop of the glycine receptor alpha1 subunit.
Language: English
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.

Journal or Publication Title: The Journal of biological chemistry
Volume: 278
Number: 19
Divisions: 10 Department of Biology
10 Department of Biology > Neurophysiology and Neurosensory Systems
?? fb10_zoologie ??
Date Deposited: 11 Apr 2011 09:45
Export:

Optionen (nur für Redakteure)

View Item View Item