NECAP2 controls clathrin coat recruitment to early endosomes for fast endocytic recycling

John P. Chamberland, Lauren T. Antonow, Michel Dias Santos, Brigitte Ritter
2016 Journal of Cell Science  
Endocytic recycling returns receptors to the plasma membrane following internalization and is essential to maintain receptor levels on the cell surface, resensitize cells to extracellular ligands and for continued nutrient uptake. Yet, the protein machineries and mechanisms driving endocytic recycling remain ill-defined. Here, we establish that NECAP2 regulates the endocytic recycling of EGFR and transferrin receptor. Our analysis of the recycling dynamics revealed that NECAP2 functions in the
more » ... ast recycling pathway that directly returns cargo from early endosomes to the cell surface. In contrast, NECAP2 does not regulate the clathrinmediated endocytosis of these cargo, the degradation of EGFR, or the recycling of transferrin along the slow, Rab11-dependent recycling pathway. We show that protein knock-down of NECAP2 leads to enlarged early endosomes and causes the loss of the clathrin adapter AP-1 from the organelle. Through structure-function analysis, we define the protein binding interfaces in NECAP2 that are critical for AP-1 recruitment to early endosomes. Together, our data identify NECAP2 as a pathway-specific regulator of clathrin coat formation on early endosomes for fast endocytic recycling.
doi:10.1242/jcs.173708 pmid:27206861 fatcat:vl6pskovrrbbniqdnqjxpty5fm