Toxin Entry: Retrograde Transport through the Secretory Pathway

The synthesis, segregation, intracellular transport, and exocytic export of secretory proteins in eukaryotic cells is now well understood. Synthesis begins on free cytosolic ribosomes that subsequently attach to the ER, resulting in the cotranslational discharge of the nascent proteins into the ER lumen. The targeting signals and the cytosolic and ER membrane components that mediate the translocation step have been extensively characterized and reviewed (for example, see 29). The ER lumen contains a range of resident proteins responsible for modifying newly synthesized polypeptides, and for ensuring correct folding into the biologically active conformation (9). Secretion entails transport of the proteins from the ER, via the Golgi stack and the TGN, to secretory vesicles that ultimately fuse with the plasma membrane to complete protein export. The secretory pathway was elucidated by Palade and his colleagues (24). Protein transport between the various compartments of the secretory...