Proposed model of AQP-1 sorting into exosomes during reticulocyte maturation. Under physiologic conditions (A), AQP-1 levels are regulated through the exosomal pathway. During osmotic stress, by contrast (B), AQP-1 secretion is inhibited, probably by regulation of its ubiquitination or by phosphorylation. It is consequently rerouted from the secretion pathway into the recycling pathway, thereby augmenting the AQP-1 concentration on the plasma membrane, and thus assisting the cell to nullify the osmotic shock. TfR trafficking, by contrast, is not affected by the osmotic disturbance and continues to be sorted and secreted through the exosomal pathway.