title: Calreticulin facilitates the cell surface expression of ABCG5/G8.
abstract: ATP-binding cassette (ABC) G5 (G5) and ABCG8 (G8) heterodimerize and function as sterol transporter that promote biliary excretion of neutral sterols. Both G5 and G8 interact with a lectin-like chaperone, calnexin (CNX), in the endoplasmic reticulum (ER) but the significance of this interaction remains unclear. Here, we show that not only CNX, but also its homologue calreticulin (CRT), is involved in the biosynthesis of G5/G8 sterol transporter. Both CNX and CRT interacted with immature forms of G5 and G8, and stimulated their productive folding by inhibiting their degradation. Interestingly, CRT predominantly enhanced the cell surface expression of mature G5/G8 whereas CNX did not have a similar effect. Inhibitors of N-glycan processing indicated that quality control of G5 and G8 might be differentially regulated in the ER. These findings clarify the role of CNX and CRT in the biosynthesis and quality control of G5/G8 sterol transporter.
authors.affiliation: Department of Molecular Medicine, Faculty of Medical and Pharmaceutical Sciences, Kumamoto University, Japan.
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Okiyoneda
authors.forename: Taijun
authors.initials: T
authors.lastname: Kono
authors.forename: Akiko
authors.initials: A
authors.lastname: Niibori
authors.forename: Kazutsune
authors.initials: K
authors.lastname: Harada
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kusuhara
authors.forename: Tappei
authors.initials: T
authors.lastname: Takada
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Shuto
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Suico
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Sugiyama
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Kai
mesh_terms: D000071018:ATP Binding Cassette Transporter, Subfamily G, Member 5; D000071019:ATP Binding Cassette Transporter, Subfamily G, Member 8; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000818:Animals; D016466:CHO Cells; D037282:Calreticulin / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism*; D006224:Cricetinae; D003412:Cricetulus; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D015870:Gene Expression / Q000502:physiology; D008074:Lipoproteins / Q000378:metabolism*
chemical_list: C416945:ABCG5 protein, human; C416946:ABCG8 protein, human; D000071018:ATP Binding Cassette Transporter, Subfamily G, Member 5; D000071019:ATP Binding Cassette Transporter, Subfamily G, Member 8; D018528:ATP-Binding Cassette Transporters; D037282:Calreticulin; D008074:Lipoproteins