title: Sorting receptor Rer1 controls surface expression of muscle acetylcholine receptors by ER retention of unassembled alpha-subunits.
abstract: 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.
authors.affiliation: Leibniz Institut für Altersforschung-Fritz Lipmann Institut, 07743 Jena, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Valkova
authors.forename: Marina
authors.initials: M
authors.lastname: Albrizio
authors.forename: Ira V
authors.initials: IV
authors.lastname: Röder
authors.forename: Michael
authors.initials: M
authors.lastname: Schwake
authors.forename: Romeo
authors.initials: R
authors.lastname: Betto
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Rudolf
authors.forename: Christoph
authors.initials: C
authors.lastname: Kaether
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport; D000483:Alleles; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism*; D015536:Down-Regulation; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D008247:Lysosomes / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000378:metabolism; D009132:Muscles / Q000378:metabolism*; D021381:Protein Transport; D011950:Receptors, Cholinergic / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D008562:Membrane Glycoproteins; D011950:Receptors, Cholinergic; D018160:Receptors, Cytoplasmic and Nuclear; C556092:Rer1 protein, mouse