Sorting receptor Rer1 controls surface expression of muscle acetylcholine receptors by ER retention of unassembled α-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 upregulated 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.protein complex | protein transport | retention/retrieval

The Importance of TM3-4 Loop Subdomains for Functional Reconstitution of Glycine Receptors by Independent Domains

“…Stepwise deletion of the complementation construct up to almost C3 (iD⌬62-TM4 to iD⌬67-TM4) resulted in a slight decrease in overall membrane expression. This decrease was coexistent with lower membrane expression of ␣1-trc, again corroborating the concomitant transport of receptor domains from the ER toward the plasma membrane (14,28). Interestingly, the amount of cell surface protein observed for iD⌬67-TM4 was indistinguishable from the other complementation constructs.…”

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