Oligomerization of pro-opiomelanocortin is independent of pH, calcium and the sorting signal for the regulated secretory pathway

Studies indicate that pro-opiomelanocortin (POMC) is sorted to the regulate d secretory pathway by binding to a sorting receptor identified as membrane -bound carboxypeptidase E (CPE) [Cool et al, (1997) Cell 88, 73-83]. The ef ficiency of this sorting mechanism could be enhanced if POMC molecules were to self-associate to form oligomers, prior or subsequent to binding to CPE . Using cross-linking and gel filtration techniques, we demonstrated that P OMC forms oligomers at both neutral and acidic pHs and calcium was not nece ssary. Delta N-POMC, which Lacks the IV-terminal sorting signal for the reg ulated secretory pathway, also formed similar oligomers, indicating that th e sorting and oligomerization domains are different. (C) 2000 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rig hts reserved.