Protein interacting with Amyloid Precursor Protein tail-1 (PAT1) is involved in early endocytosis

• Published in: Cellular and molecular life sciences : CMLS 2019-12, Vol.76 (24), p.4995-5009
• Main Authors: Dilsizoglu Senol, Aysegul, Tagliafierro, Lidia, Gorisse-Hussonnois, Lucie, Rebeillard, Florian, Huguet, Léa, Geny, David, Contremoulins, Vincent, Corlier, Fabian, Potier, Marie-Claude, Chasseigneaux, Stéphanie, Darmon, Michèle, Allinquant, Bernadette
• Format: Article
• Language: English
• Subjects: Alzheimer's disease; Amino Acid Transport Systems - genetics; Amyloid beta-Protein Precursor - genetics; Amyloid precursor protein; Androgen receptors; Animals; Biochemistry; Biomedical and Life Sciences; Biomedicine; Cell Biology; Cell Membrane - genetics; Cell Membrane - metabolism; Cell surface; Endocytosis; Endocytosis - genetics; Endosomes - genetics; Endosomes - metabolism; Gene Expression Regulation; Humans; Life Sciences; Low level; Mice; Neurons - metabolism; Original; Original Article; Precursors; Protein Transport; Protein turnover; Proteins; rab GTP-Binding Proteins - genetics; rab4 GTP-Binding Proteins - genetics; rab5 GTP-Binding Proteins - genetics; rab7 GTP-Binding Proteins; Receptors, Androgen - genetics; Symporters - genetics; Transferrin; Transferrins; Vesicles; Vesicular Transport Proteins - genetics
• ISSN: 1420-682X; 1420-9071
• DOI: 10.1007/s00018-019-03157-7

Protein interacting with Amyloid Precursor Protein (APP) tail 1 (PAT1) also called APPBP2 or Ara 67 has different targets such as APP or androgen receptor and is expressed in several tissues. PAT1 is known to be involved in the subcellular trafficking of its targets. We previously observed in primary neurons that PAT1 is poorly associated with APP at the cell surface. Here we show that PAT1 colocalizes with vesicles close to the cell surface labeled with Rab5, Rab4, EEA1 and Rabaptin-5 but not with Rab11 and Rab7. Moreover, PAT1 expression regulates the number of EEA1 and Rab5 vesicles, and endocytosis/recycling of the transferrin receptor. In addition, low levels of PAT1 decrease the size of transferrin-colocalized EEA1 vesicles with time following transferrin uptake. Finally, overexpression of the APP binding domain to PAT1 is sufficient to compromise endocytosis. Altogether, these data suggest that PAT1 is a new actor in transferrin early endocytosis. Whether this new function of PAT1 may have consequences in pathology remains to be determined.