Calreticulin facilitates the cell surface expression of ABCG5/G8.
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.
Okiyoneda
Tsukasa
T
Department of Molecular Medicine, Faculty of Medical and Pharmaceutical Sciences, Kumamoto University, Japan.
Kono
Taijun
T
Niibori
Akiko
A
Harada
Kazutsune
K
Kusuhara
Hiroyuki
H
Takada
Tappei
T
Shuto
Tsuyoshi
T
Suico
Mary Ann
MA
Sugiyama
Yuichi
Y
Kai
Hirofumi
H
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*
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