Basolateral sorting of the coxsackie and adenovirus receptor through interaction of a canonical YXXΦ motif with the clathrin adaptors AP-1A and AP-1B

• DOI: 10.1073/pnas.1117949109
• Publication Date: 2012-02-17T05:44:39Z
• Authors: Jose Maria Carvaj...; Diego Gravotta; Rafael Mattera; Fernando Diaz; Andres Perez Bay; Angel C. Roman; Ryan P. Schreiner; Roland Thuenauer; Juan S. Bonifacino; Enrique Rodriguez...
• Keywords: Coxsackie and Adenovirus Receptor-Like Membrane Protein; 0303 health sciences; Ranidae; Protein Conformation; Adaptor Protein Complex 1; Amino Acid Motifs; Cell Membrane; Green Fluorescent Proteins; Adaptor Protein Complex 2; Fishes; Epithelial Cells; Endosomes; Clathrin; Endocytosis; Exocytosis; Cell Line; 3. Good health; Protein Transport; 03 medical and health sciences; Dogs; Mutation; Animals; Humans

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.