Fig. 8.

Model of retromer-dependent and SNX27–retromer-dependent plasma membrane recycling of CTR1 and ATP7A, respectively. In response to elevated copper or exposure to platinum-based drugs, such as cisplatin, CTR1 is endocytosed from the plasma membrane and sequestered on retromer-positive endosomes. In prolonged high copper or cisplatin conditions, CTR1 remains associated with the maturing endosome. Elevated copper in the cell upregulates SNX27-retromer-dependent ATP7A trafficking from endosomes to the plasma membrane and/or to the TGN for re-secretion to expel excess copper. Upon removal of extracellular copper or cisplatin, CTR1 is recycled back to the plasma membrane in a retromer-dependent manner and ATP7A trafficking between the TGN and plasma membrane is returned to constitutive levels.