AP-4 binds basolateral signals and participates in basolateral sorting in epithelial MDCK cells.
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.
Simmen
Thomas
T
Institute of Biochemistry, University of Lausanne, CH-1066 Epalinges, Switzerland.
Höning
Stefan
S
Icking
Ann
A
Tikkanen
Ritva
R
Hunziker
Walter
W
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
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