Receptor-Mediated Endocytosis of Plasminogen Activators

Regulation of intracellular protein trafficking is one of the central issues in cell biology. Extracellular proteins are delivered to cells through endocytosis wherein, in general, seven major classes of trafficking events are involved: nutrient uptake, protein clearance, transcytosis, growth factor uptake, virus entry, toxin entry, and antigen uptake and processing. Smaller molecules are delivered to cells across the membrane through water-filled channels, carriers, or transporters. In addition, some small molecules are taken up through caveolae in a process termed “potucytusis,” which bears many similarities to endocytosis. The initial step in receptor-mediated endocytosis involves the invagination of plasma membrane into coated pits by the progressive generation of membrane curvature mediated by a specialized set of membrane-associated proteins. As the membrane becomes sufficiently curved, the opposing regions of the membrane ultimately fuse creating an endocytic vesicle (the coated vesicle) in which the internal contents are now discrete from the extracellular milieu. Simultaneously, the pH within the vesicle falls.