1. The Clathrin Adaptor AP-1A Mediates Basolateral Polarity
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Enrique Rodriguez-Boulan, Rafael Mattera, Jason R. Banfelder, Sylvie Deborde, Diego Gravotta, Juan S. Bonifacino, and Jose Maria Carvajal-Gonzalez
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Endosome ,Adaptor Protein Complex 1 ,Fluorescent Antibody Technique ,Endosomes ,Biology ,medicine.disease_cause ,Clathrin ,General Biochemistry, Genetics and Molecular Biology ,Article ,03 medical and health sciences ,symbols.namesake ,0302 clinical medicine ,Dogs ,Two-Hybrid System Techniques ,Protein targeting ,Cell polarity ,Receptors, Transferrin ,medicine ,Animals ,RNA, Small Interfering ,Molecular Biology ,Cells, Cultured ,030304 developmental biology ,Epithelial polarity ,0303 health sciences ,Cell Membrane ,Cell Polarity ,Epithelial Cells ,Cell Biology ,Golgi apparatus ,Transport protein ,Cell biology ,Protein Transport ,Receptors, LDL ,symbols ,biology.protein ,Clathrin adaptor proteins ,030217 neurology & neurosurgery ,Developmental Biology ,trans-Golgi Network - Abstract
SummaryClathrin 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.
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