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

Cell Mol Life Sci. 2019 Dec;76(24):4995-5009. doi: 10.1007/s00018-019-03157-7. Epub 2019 May 28.

Abstract

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.

Keywords: Caspase cleaved APP; Endocytosis; Neuron; PAT1; Transferrin uptake.

MeSH terms

  • Amino Acid Transport Systems / genetics*
  • Amyloid beta-Protein Precursor / genetics
  • Animals
  • Cell Membrane / genetics
  • Cell Membrane / metabolism
  • Endocytosis / genetics
  • Endosomes / genetics
  • Endosomes / metabolism
  • Gene Expression Regulation
  • Humans
  • Mice
  • Neurons / metabolism
  • Protein Transport
  • Receptors, Androgen / genetics
  • Symporters / genetics*
  • Vesicular Transport Proteins / genetics
  • rab GTP-Binding Proteins / genetics
  • rab4 GTP-Binding Proteins / genetics
  • rab5 GTP-Binding Proteins / genetics

Substances

  • Amino Acid Transport Systems
  • Amyloid beta-Protein Precursor
  • Rabep1 protein, mouse
  • Receptors, Androgen
  • Slc36a1 protein, mouse
  • Symporters
  • Vesicular Transport Proteins
  • early endosome antigen 1
  • rab7 protein
  • rab11 protein
  • rab GTP-Binding Proteins
  • rab4 GTP-Binding Proteins
  • rab5 GTP-Binding Proteins