title: A transmembrane motif governs the surface trafficking of nicotinic acetylcholine receptors.
abstract: Surface expression of the nicotinic acetylcholine receptor (AChR) requires the assembly of multiple subunits in the endoplasmic reticulum (ER). Little is known, however, about the mechanism by which assembled receptor pentamers are transported to the cell membrane while unassembled subunits are retained in the ER. Here we report that a motif conserved in the transmembrane domain of AChR subunits is critically involved in this process. In COS cells, mutation within this signal allowed surface expression of unassembled subunits. Conversely, insertion of the sequence to unrelated proteins that are normally transported to the surface resulted in ER retention. The signal is buried in AChR pentamers, but is exposed on unassembled subunits in the ER, where it promotes protein degradation. We therefore conclude that this signal ensures surface trafficking of only functional AChRs.
authors.affiliation: Department of Neurobiology, University of Pittsburgh School of Medicine, 3500 Terrace Street, Pittsburgh, Pennsylvania 15261, USA.
authors.forename: Jun-Mei
authors.initials: JM
authors.lastname: Wang
authors.forename: Lili
authors.initials: L
authors.lastname: Zhang
authors.forename: Yun
authors.initials: Y
authors.lastname: Yao
authors.forename: Nitnara
authors.initials: N
authors.lastname: Viroonchatapan
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Rothe
authors.forename: Zuo-Zhong
authors.initials: ZZ
authors.lastname: Wang
mesh_terms: D020816:Amino Acid Motifs / Q000502:physiology; D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002462:Cell Membrane / Q000378:metabolism / Q000502:physiology; D004721:Endoplasmic Reticulum / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D021122:Protein Subunits; D021381:Protein Transport / Q000502:physiology; D011978:Receptors, Nicotinic / Q000737:chemistry / Q000502:physiology*
chemical_list: D021122:Protein Subunits; D011978:Receptors, Nicotinic