MODULATION OF INTRACELLULAR-TRANSPORT BY TRANSPORTED PROTEINS - INSIGHT FROM REGULATION OF COPI-MEDIATED TRANSPORT

Intracellular transport is best understood for how proteins are shuttl ed among different compartments of the secretory pathway by membrane-b ound transport carriers. However, it remains unclear whether regulatio n of this transport is modulated by the transported (cargo) proteins i n the lumen of transport pathways, In the early secretory pathways tha t connect the endoplasmic reticulum (ER) and the Golgi complex, the sm all GTPase ADP-ribosylation factor 1 (ARF1) recruits a cytosolic coat protein complex named COPI onto membranes as a key step in the formati on of transport vesicles, Transport of newly synthesized proteins that leave the ER includes a class of cargo proteins with a sequence motif of KDEL. When these KDEL proteins leave the ER to reach the Golgi com plex, they are recognized by their receptor and transported retrograde in COPI-coated vesicles back to the ER, We now demonstrate that stimu lation of the I(DEL receptor by a KDEL protein enhances an interaction between the I(DEL receptor and a GTPase-activating protein for ARF1. As a result, more cytosolic GTPase-activating protein is recruited to membranes to inactivate ARF1, Thus, the KDEL proteins are examples of luminal cargo proteins that regulate transport by activating their rec eptor. Most likely, this regulation affects retrograde transport from the Golgi complex to the ER, as activated KDEL receptor appears to res ide only in retrograde COPI-coated vesicles.