fig2

Figure 2. TGN lumenal sorting mechanisms. Motifs that are required for the sorting of RSP proteins to DCVs. These include (A) the interaction between vasopressin and neurophysin domains in their precursor form; (B) disulfide bond; (C) charged α-helices; (D) the sorting signal motif of POMC that is conformation-dependent and comprises of two acidic residues, Asp10 and Glu14, and the two hydrophobic residues, Leu11 and Leu18. (Figure reproduced from Cawley et al. with permission)^[27]; (E) The sorting mechanism for POMC, pro-enkephalin, and BDNF use similar sorting motifs comprising of a pair of acidic amino acids binding to a pair of basic amino acids in a sorting receptor, membrane CPE which associates specifically with cholesterol-sphingolipid-rich lipid raft domains at the TGN membrane prior to budding off to form a DCV. (F) RSP proteins can also be sorted to the RSP by aggregation at pH 5-6 and 1-10 mM Ca²⁺ inside the TGN lumen. TGN: trans-Golgi network; POMC: pro-opiomelanocortin; BDNF: brain-derived neurotrophic factor; CPE: carboxypeptidase E; DCV: dense core vesicles.