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![Trafficking of hormones and trophic factors to secretory and extracellular vesicles: a historical perspective and new hypothesis](https://image.oaes.cc/ccc1d523-ad7c-487d-92d9-dd32f5425776/evcna4034.fig.5.jpg)
Figure 5. Sorting of RSP proteins into DCV by retention and constitutive-like secretion. RSP proteins can be packaged into DCVs by a “sorting-by-retention” mechanism: C-terminal disulfide bond is necessary for proTRH to remain in RSP vesicles (A); Non-RSP proteins in immature DCVs are removed by constitutive-like secretory pathways. AP-1 binds to the cytoplasmic tails of furin and M6PR and removes furin and M6PR from immature DCV via clathrin-mediated constitutive-like secretion (B). Golgi-localized, γ-ear containing ADP-ribosylation factor binding (GGA) mediates the removal of VAMP4 from immature DCVs (B); APS1 increases the activity of H-ATPase on DCVs to facilitate vesicle acidification. Rbcn3 promotes the translocation of CAPS1 to DCVs from the cytoplasm (C). proTRH: prothyrotropin-releasing hormone; M6PR: mannose-6-phosphate receptor; Rbcn3: rabconnectin 3; DCV: dense core vesicles; RSP: regulated secretory pathway.