Synthetic peptides of the Rab effector domain inhibit vesicular transport through the secretory pathway

Synthetic peptides of the putative effector domain of members of the ras‐related rab gene family of small GTP‐binding proteins were synthesized and found to be potent inhibitors of endoplasmic reticulum (ER) to Golgi and intra‐Golgi transport in vitro. Inhibition of transport by one of the effector domain peptides was rapid (t1/2 of 30 s), and irreversible. Analysis of the temporal site of peptide inhibition indicated that a late step in transport was blocked, coincident with a Ca2(+)‐dependent prefusion step. The results provide novel biochemical evidence for the role of members of the rab gene family in vesicular transport in mammalian cells, and implicate a role for a new downstream Rab effector protein (REP) regulating vesicle fusion.