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.
Plutner
H
H
Department of Molecular Biology, Research Institute of Scripps Clinic, La Jolla, CA 92037.
Schwaninger
R
R
Pind
S
S
Balch
W E
WE
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000235:genetics*; D006056:Golgi Apparatus / Q000187:drug effects / Q000378:metabolism*; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006160:Guanosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D007700:Kinetics; D008954:Models, Biological; D008969:Molecular Sequence Data; D005810:Multigene Family; D010455:Peptides / Q000138:chemical synthesis / Q000494:pharmacology*; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D012689:Sequence Homology, Nucleic Acid; D013873:Thionucleotides / Q000494:pharmacology
D010455:Peptides; D011518:Proto-Oncogene Proteins; D013873:Thionucleotides; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006160:Guanosine Triphosphate; D019204:GTP-Binding Proteins; D016283:Proto-Oncogene Proteins p21(ras)