title: Basolateral sorting of the coxsackie and adenovirus receptor through interaction of a canonical YXXPhi motif with the clathrin adaptors AP-1A and AP-1B.
abstract: The coxsackie and adenovirus receptor (CAR) plays key roles in epithelial barrier function at the tight junction, a localization guided in part by a tyrosine-based basolateral sorting signal, (318)YNQV(321). Sorting motifs of this type are known to route surface receptors into clathrin-mediated endocytosis through interaction with the medium subunit (μ2) of the clathrin adaptor AP-2, but how they guide new and recycling membrane proteins basolaterally is unknown. Here, we show that YNQV functions as a canonical YxxΦ motif, with both Y318 and V321 required for the correct basolateral localization and biosynthetic sorting of CAR, and for interaction with a highly conserved pocket in the medium subunits (μ1A and μ1B) of the clathrin adaptors AP-1A and AP-1B. Knock-down experiments demonstrate that AP-1A plays a role in the biosynthetic sorting of CAR, complementary to the role of AP-1B in basolateral recycling of this receptor. Our study illustrates how two clathrin adaptors direct basolateral trafficking of a plasma membrane protein through interaction with a canonical YxxΦ motif.
authors.affiliation: Department of Ophthalmology, Margaret Dyson Vision Research Institute, Weill Cornell Medical College, New York, NY 10065, USA.
authors.forename: Jose Maria
authors.initials: JM
authors.lastname: Carvajal-Gonzalez
authors.forename: Diego
authors.initials: D
authors.lastname: Gravotta
authors.forename: Rafael
authors.initials: R
authors.lastname: Mattera
authors.forename: Fernando
authors.initials: F
authors.lastname: Diaz
authors.forename: Andres
authors.initials: A
authors.lastname: Perez Bay
authors.forename: Angel C
authors.initials: AC
authors.lastname: Roman
authors.forename: Ryan P
authors.initials: RP
authors.lastname: Schreiner
authors.forename: Roland
authors.initials: R
authors.lastname: Thuenauer
authors.forename: Juan S
authors.initials: JS
authors.lastname: Bonifacino
authors.forename: Enrique
authors.initials: E
authors.lastname: Rodriguez-Boulan
mesh_terms: D033961:Adaptor Protein Complex 1 / Q000737:chemistry*; D033962:Adaptor Protein Complex 2 / Q000737:chemistry; D020816:Amino Acid Motifs; D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002966:Clathrin / Q000737:chemistry; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D004285:Dogs; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology; D005089:Exocytosis; D005399:Fishes; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D009154:Mutation; D011487:Protein Conformation; D021381:Protein Transport; D011898:Ranidae; D011991:Receptors, Virus / Q000737:chemistry*
chemical_list: D033961:Adaptor Protein Complex 1; D033962:Adaptor Protein Complex 2; C568771:CLMP protein, human; D002966:Clathrin; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D011991:Receptors, Virus; D049452:Green Fluorescent Proteins