Constitutively secreted proteins have traditionally been believed to b
e excluded from the regulated secretory pathway. In this work we show
that kappa light chain and Fc fragment two markers of the constitutive
pathway, are present in the regulated pathway in AtT-2O cells. They c
olocalize with the endogenous hormone ACTH and they exhibit stimulus-d
ependent secretion. The Fc fragment, which undergoes intracellular tra
nsport at the same rate as the ACTH precursor POMC, enters the forming
secretory granules, however, it is partially lost during granule matu
ration. These observations show that classic constitutive secretory ma
rkers are not excluded from the regulated secretory pathway and that e
fficient sorting for regulated secretion occurs above a background of
proteins which enter the granules without sorting. (C) 1998 Federation
of European Biochemical Societies.