Diphtheria Toxin as a Molecular Tool in the Study of Acidic Fibroblast Growth Factor Signalling

: In eukaryotic cells proteins are translocated across a number of cellular membranes into various intracellular organelles such as the endoplasmatic reticulum, mitochondria, peroxisomes and chloroplasts. In all these cases the proteins are translocated away from the cytosol. However, certain proteins are also translocated in the opposite direction, from the exterior to the cytosol. Well established examples are some bacterial and plant protein toxins, that exert their effect in the cytosol. A common property of protein toxins with intracellular action is that they contain two functionally different moieties, in many cases consisting of two. disulfide-linked polypeptides. Relatively little is known about how these proteins cross the membrane. The translocation process is best understood in the case of diphtheria toxin, which binds to cell surface receptors, is then taken up by endocytosis and is subsequently translocated to the cytosol, where it inactivates elongation factor 2. Recently it has been recognized that diphtheria toxin as well as a few other protein toxins can be used to carry passenger peptides or proteins into cells (in addition to other usefull roles which the toxins have begun to play in understanding many cellular processes and in certain prophylactic and therapeutic purposes). Here, the approach of using diphtheria toxin as a translocation vehicle in the study of new aspects of signal transduction mechanisms activated by acidic fibroblast growth factor is discussed and the possibility that some proteins have distinct functions in more than one cellular compartment is considered. Finally, this article focuses on the role of the toxins as tools in cell biology and experimental medicine.