title: The clathrin adaptor AP-1A mediates basolateral polarity.
abstract: Clathrin and the epithelial-specific clathrin adaptor AP-1B mediate basolateral trafficking in epithelia. However, several epithelia lack AP-1B, and mice knocked out for AP-1B are viable, suggesting the existence of additional mechanisms that control basolateral polarity. Here, we demonstrate a distinct role of the ubiquitous clathrin adaptor AP-1A in basolateral protein sorting. Knockdown of AP-1A causes missorting of basolateral proteins in MDCK cells, but only after knockdown of AP-1B, suggesting that AP-1B can compensate for lack of AP-1A. AP-1A localizes predominantly to the TGN, and its knockdown promotes spillover of basolateral proteins into common recycling endosomes, the site of function of AP-1B, suggesting complementary roles of both adaptors in basolateral sorting. Yeast two-hybrid assays detect interactions between the basolateral signal of transferrin receptor and the medium subunits of both AP-1A and AP-1B. The basolateral sorting function of AP-1A reported here establishes AP-1 as a major regulator of epithelial polarity.
authors.affiliation: Margaret Dyson Vision Research Institute, Department of Ophthalmology, Weill Cornell Medical College, New York, NY 10065, USA. dig2003@med.cornell.edu
authors.forename: Diego
authors.initials: D
authors.lastname: Gravotta
authors.forename: Jose Maria
authors.initials: JM
authors.lastname: Carvajal-Gonzalez
authors.forename: Rafael
authors.initials: R
authors.lastname: Mattera
authors.forename: Sylvie
authors.initials: S
authors.lastname: Deborde
authors.forename: Jason R
authors.initials: JR
authors.lastname: Banfelder
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 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D016764:Cell Polarity; D002478:Cells, Cultured; D002966:Clathrin / Q000378:metabolism*; D004285:Dogs; D011992:Endosomes / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D021381:Protein Transport; D034741:RNA, Small Interfering / Q000235:genetics; D011973:Receptors, LDL / Q000378:metabolism; D011990:Receptors, Transferrin / Q000378:metabolism; D020798:Two-Hybrid System Techniques; D021601:trans-Golgi Network / Q000502:physiology*
chemical_list: D033961:Adaptor Protein Complex 1; D002966:Clathrin; D034741:RNA, Small Interfering; D011973:Receptors, LDL; D011990:Receptors, Transferrin