title: Rer1p regulates the ER retention of immature rhodopsin and modulates its intracellular trafficking.
abstract: Rhodopsin is a pigment in photoreceptor cells. Some rhodopsin mutations cause the protein to accumulate in the endoplasmic reticulum (ER), leading to photoreceptor degeneration. Although several mutations have been reported, how mutant rhodopsin is retained in the ER remains unclear. In this study, we identified Rer1p as a modulator of ER retention and rhodopsin trafficking. Loss of Rer1p increased the transport of wild-type rhodopsin to post-Golgi compartments. Overexpression of Rer1p caused immature wild-type rhodopsin to accumulate in the ER. Interestingly, the G51R rhodopsin mutant, which has a mutation in the first transmembrane domain and accumulates in the ER, was released to the plasma membrane or lysosomes in Rer1-knockdown cells. Consistent with these results, Rer1p interacted with both wild-type and mutant rhodopsin. These results suggest that Rer1p regulates the ER retention of immature or misfolded rhodopsin and modulates its intracellular trafficking through the early secretory pathway.
authors.affiliation: 1] Laboratory of Molecular Traffic, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Gunma 371-8512, Japan [2].
authors.forename: Akinori
authors.initials: A
authors.lastname: Yamasaki
authors.affiliation: Laboratory of Molecular Traffic, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Gunma 371-8512, Japan.
authors.forename: Taichi
authors.initials: T
authors.lastname: Hara
authors.affiliation: Laboratory of Molecular Traffic, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Gunma 371-8512, Japan.
authors.forename: Ikuko
authors.initials: I
authors.lastname: Maejima
authors.affiliation: 1] Laboratory of Molecular Traffic, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Gunma 371-8512, Japan [2] Laboratory of Molecular Membrane Biology, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Gunma 371-8512, Japan.
authors.forename: Miyuki
authors.initials: M
authors.lastname: Sato
authors.affiliation: Laboratory of Molecular Traffic, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Gunma 371-8512, Japan.
authors.forename: Katsuya
authors.initials: K
authors.lastname: Sato
authors.affiliation: Laboratory of Molecular Traffic, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Gunma 371-8512, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Sato
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport; D019943:Amino Acid Substitution; D002462:Cell Membrane / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006056:Golgi Apparatus / Q000378:metabolism*; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D008247:Lysosomes / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D010766:Phosphorylation; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012243:Rhodopsin / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D008562:Membrane Glycoproteins; C109546:RER1 protein, human; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins; D012243:Rhodopsin
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