Sorting receptor Rer1 controls surface expression of muscle acetylcholine receptors by ER retention of unassembled alpha-subunits
| Autor: | Ira V. Röder, Christina Valkova, Marina Albrizio, Christoph Kaether, Michael Schwake, Romeo Betto, Rüdiger Rudolf |
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| Rok vydání: | 2010 |
| Předmět: |
Down-Regulation
Receptors Cytoplasmic and Nuclear Mice Transgenic Biology Endoplasmic Reticulum Mice Muscarinic acetylcholine receptor M5 medicine Myocyte Animals Receptors Cholinergic Receptor Muscle Skeletal Alleles Acetylcholine receptor Multidisciplinary Membrane Glycoproteins Myogenesis Reverse Transcriptase Polymerase Chain Reaction Muscles Cell Membrane Skeletal muscle ER retention Biological Sciences Molecular biology Cell biology Up-Regulation Nicotinic acetylcholine receptor Adaptor Proteins Vesicular Transport Protein Transport medicine.anatomical_structure Lysosomes |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America, 108(2): 621-625 |
| ISSN: | 1091-6490 |
| Popis: | The nicotinic acetylcholine receptor of skeletal muscle is composed of five subunits that are assembled in a stepwise manner. Quality control mechanisms ensure that only fully assembled receptors reach the cell surface. Here, we show that Rer1, a putative Golgi-ER retrieval receptor, is involved in the biogenesis of acetylcholine receptors. Rer1 is expressed in the early secretory pathway in the myoblast line C2C12 and in mouse skeletal muscle, and up-regulated during myogenesis. Upon down-regulation of Rer1 in C2C12 cells, unassembled acetylcholine receptor α-subunits escape from the ER and are transported to the plasma membrane and lysosomes, where they are degraded. As a result, the amount of fully assembled receptor at the cell surface is reduced. In vivo Rer1 knockdown and genetic inactivation of one Rer1 allele lead to significantly smaller neuromuscular junctions in mice. Our data show that Rer1 is a functionally important unique factor that controls surface expression of muscle acetylcholine receptors by localizing unassembled α-subunits to the early secretory pathway. |
| Databáze: | OpenAIRE |
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