title: AP-4 binds basolateral signals and participates in basolateral sorting in epithelial MDCK cells.
abstract: Adaptors are heterotetrameric complexes that mediate the incorporation of cargo into transport vesicles by interacting with sorting signals present in the cytosolic domain of transmembrane proteins. Four adaptors, AP-1 (beta 1, gamma, mu 1A or mu 1B, sigma 1), AP-2 (beta 2, alpha, mu 2, sigma 2), AP-3 (beta 3 , delta, mu 3, sigma 3) or AP-4 (beta 4, epsilon, mu 4, sigma 4), have been characterized. AP-1 and AP-3 mediate sorting events at the level of the TGN and/or endosomes, whereas AP-2 functions in endocytic clathrin coated vesicle formation; no function is known so far for AP-4. Here, we show that AP-4 can bind different types of cytosolic signals known to mediate basolateral transport in epithelial cells. Furthermore, in MDCK cells with depleted mu 4 protein levels, several basolateral proteins are mis-sorted to the apical surface, showing that AP-4 participates in basolateral sorting in epithelial cells.
authors.affiliation: Institute of Biochemistry, University of Lausanne, CH-1066 Epalinges, Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Simmen
authors.forename: Stefan
authors.initials: S
authors.lastname: Höning
authors.forename: Ann
authors.initials: A
authors.lastname: Icking
authors.forename: Ritva
authors.initials: R
authors.lastname: Tikkanen
authors.forename: Walter
authors.initials: W
authors.lastname: Hunziker
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport; D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002458:Cell Fractionation; D002460:Cell Line; D016764:Cell Polarity; D004285:Dogs; D004847:Epithelial Cells / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D007668:Kidney / Q000166:cytology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D034041:Monomeric Clathrin Assembly Proteins; D011485:Protein Binding; D021122:Protein Subunits; D021381:Protein Transport / Q000502:physiology*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D002352:Carrier Proteins; D008565:Membrane Proteins; D034041:Monomeric Clathrin Assembly Proteins; D021122:Protein Subunits; D016271:Proto-Oncogene Proteins c-myc; D011993:Recombinant Fusion Proteins; C439023:clathrin assembly protein AP180