Vesicular tubular clusters between the ER and Golgi mediate concentration of soluble secretory proteins by exclusion front COPI-coated vesicles

We have determined the concentrations of the secretory proteins amylase and chymotrypsinogen and the membrane proteins KDELr and rBet1 in COPII- and C OPI-coated pre-Golgi compartments of pancreatic cells by quantitative immun oelectron microscopy. COPII was confined to ER membrane buds and adjacent v esicles. COPI occurred on vesicular tubular clusters (VTCs), Golgi cisterna e, the trans-Golgi network, and immature secretory granules. Both secretory proteins exhibited a first, significant concentration step in noncoated se gments of VTC tubules and were excluded from COPI-coated tips. By contrast, KDELr and rBet1 showed a first, significant concentration in COPII-coated ER buds and vesicles and were prominently present in COPI-coated tips of VT C tubules. These data suggest an important role of VTCs in soluble cargo co ncentration by exclusion from COPI-coated domains.