Proteasomal degradation of ?-aminobutyric acidB receptors is mediated by the interaction of the GABAB2 C terminus with the proteasomal ATPase Rtp6 and regulated by neuronal activity
| Autor: | Khaled Zemoura, Dietmar Benke |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Proteasome Endopeptidase Complex
Enzyme-Linked Immunosorbent Assay Biology Endoplasmic-reticulum-associated protein degradation Protein degradation GABAB receptor Endoplasmic Reticulum Biochemistry Mice Neurobiology Neurotransmitter receptor Two-Hybrid System Techniques Animals Homeostasis Humans Rats Wistar Receptor Molecular Biology Transcription factor Adaptor Proteins Signal Transducing Adenosine Triphosphatases Neurons Neuronal Plasticity Ubiquitin GABAA receptor Lysine Cell Membrane Cell Biology LIM Domain Proteins Protein Structure Tertiary Rats Cell biology HEK293 Cells Gene Expression Regulation Receptors GABA-B Proteasome nervous system Mutation Synapses ATPases Associated with Diverse Cellular Activities Protein Binding Transcription Factors |
| Zdroj: | The Journal of Biological Chemistry |
| DOI: | 10.1074/jbc.M113.541987 |
| Popis: | Regulation of cell surface expression of neurotransmitter receptors is crucial for determining synaptic strength and plasticity, but the underlying mechanisms are not well understood. We previously showed that proteasomal degradation of GABAB receptors via the endoplasmic reticulum (ER)-associated protein degradation (ERAD) machinery determines the number of cell surface GABAB receptors and thereby GABAB receptor-mediated neuronal inhibition. Here, we show that proteasomal degradation of GABAB receptors requires the interaction of the GABAB2 C terminus with the proteasomal AAA-ATPase Rpt6. A mutant of Rpt6 lacking ATPase activity prevented degradation of GABAB receptors but not the removal of Lys(48)-linked ubiquitin from GABAB2. Blocking ERAD activity diminished the interaction of Rtp6 with GABAB receptors resulting in increased total as well as cell surface expression of GABAB receptors. Modulating neuronal activity affected proteasomal activity and correspondingly the interaction level of Rpt6 with GABAB2. This resulted in altered cell surface expression of the receptors. Thus, neuronal activity-dependent proteasomal degradation of GABAB receptors by the ERAD machinery is a potent mechanism regulating the number of GABAB receptors available for signaling and is expected to contribute to homeostatic neuronal plasticity. |
| Databáze: | OpenAIRE |
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