Figure 2. ARC topological paradox.
NAADP and cADPR are cytosolic messengers targeting channels in the ER (RyR receptors) or in acidic vesicles (TPCs). Paradoxically, ARCs in general, have a “targeted for secretion” signal peptide and are found in the plasma membrane or in the lumen of secretory vesicles (Type II transmembrane protein orientation). Putative nucleoside transporters would be responsible for transporting the messengers to the cytoplasm. In human lymphocytes, ARCs were also found in an alternative orientation (Type III), with the C-terminal facing the cytoplasm.