Road Rage

Abstract

Ras-related low molecular weight guanosine triphosphatases (GTPases) regulate nearly all aspects of cell physiology including growth, differentiation, proliferation, cell movement, and nuclear transport. The Rab family of GTPases regulates another aspect of physiology: the transport of membranes throughout the cell.1–5 There are at least 30 members of the Rab family in mammalian species, and different Rabs regulate different aspects of tubulovesicular trafficking.1,2 For example, Rab1 regulates the transport of newly synthesized proteins from the rough endoplasmic reticulum (ER) to the Golgi in the exocytic pathway1–5 (Figure). Most secreted proteins and transmembrane receptors pass through this exocytic pathway. Rough ER-to-Golgi transport initially involves the formation of vesicles from the ER under the direction of a protein coat called COPII.5 The COPII coat bends the ER membrane so that it pinches off as a vesicle (Figure). The vesicle quickly loses its protein coat and then moves along microtubule tracks to the cis -Golgi complex where the vesicle fuses and delivers its protein cargo.4 Secretory and membrane proteins then sequentially travel through the cis , medial, and trans compartments of the Golgi complex during which the proteins undergo posttranslational modifications before their transit to the extracellular space or to the plasma membrane. Model of Rab1-regulated rough ER-to-Golgi protein trafficking. Newly synthesized proteins in the ER trigger the formation of vesicles that bud off and travel to the Golgi stacks. Budding is promoted by the formation of a COPII protein coat that bends the ER membrane. Rab1-GTP regulates vesicular targeting to the Golgi complex and also regulates vesicular fusion. Rab1-GTP may act …