It has been proposed that unconjugated type I ribosome-inactivating proteins (RIP) enter cells through passive mechanisms such as fluid-phase pinocytosis. However, some observations, such as the difference in sensitivity to type I RIP among different cell types, and the organ-specific toxicity of type I RIP, indicate a specific mechanism for the entry of these proteins into target cells. The α2-macroglobulin receptor (α2MR) is responsible for the binding and endocytosis of several ligands, including α2-macroglobulin-proteinase complexes, plasminogen-activator-inhibitor complexes, apoE-enriched β-very low density lipoproteins, and lipoprotein lipase. Here we demonstrate that saporin, a potent type I RIP, binds specifically to purified α2MR and the binding is prevented by some α2MR ligands. Moreover, the occupancy of specific ligand-binding sites on cell surface α2MR decreases the cytotoxicity of saporin. The A chain of ricin, a type II RIP, also interacts with α2MR. This, and the fact that saporin and ricin A chain both interact: also with α2-macroglobulin, indicates a general mechanism of complex interactions between RIP and cellular membranes that is mediated by α2-macroglobulin and the α2MR system.
|Number of pages||7|
|Journal||European Journal of Biochemistry|
|Publication status||Published - 1995|
- α-Macroglobulin receptor
- Ribosome-inactivating protein
ASJC Scopus subject areas