title: Di-acidic motifs in the membrane-distal C termini modulate the transport of angiotensin II receptors from the endoplasmic reticulum to the cell surface.
abstract: The molecular mechanisms underlying the endoplasmic reticulum (ER) export and cell surface transport of nascent G protein-coupled receptors (GPCRs) have just begun to be revealed and previous studies have shown that hydrophobic motifs in the putative amphipathic 8(th) α-helical region within the membrane-proximal C termini play an important role. In this study, we demonstrate that di-acidic motifs in the membrane-distal, nonstructural C-terminal portions are required for the exit from the ER and transport to the plasma membrane of angiotensin II receptors, but not adrenergic receptors. More interestingly, distinct di-acidic motifs dictate optimal export trafficking of different angiotensin II receptors and export ability of each acidic residue in the di-acidic motifs cannot be fully substituted by other acidic residue. Moreover, the function of the di-acidic motifs is likely mediated through facilitating the recruitment of the receptors onto the ER-derived COPII transport vesicles. Therefore, the di-acidic motifs located in the membrane-distal C termini may represent the first linear motifs which recruit selective GPCRs onto the COPII vesicles to control their export from the ER.
authors.affiliation: Department of Pharmacology and Experimental Therapeutics, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112, USA.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Zhang
authors.forename: Chunmin
authors.initials: C
authors.lastname: Dong
authors.forename: Qiong J
authors.initials: QJ
authors.lastname: Wu
authors.forename: William E
authors.initials: WE
authors.lastname: Balch
authors.forename: Guangyu
authors.initials: G
authors.lastname: Wu
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D022181:COP-Coated Vesicles / Q000235:genetics / Q000378:metabolism*; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D016716:PC12 Cells; D021381:Protein Transport / Q000502:physiology; D051381:Rats; D011945:Receptors, Angiotensin / Q000235:genetics / Q000378:metabolism*
chemical_list: D011945:Receptors, Angiotensin