Targeting Talk: Retrograde Transport

Q: I’m trying to find out if enough Anti-DBH-SAP will be retrogradely transported and taken up by non targeted sympathetic neurons by bulk fluid-phase endocytosis. Does saporin become degraded after it kills the neuron or does it enter the extracellular matrix?

A: It is very unlikely that a targeted toxin such as Anti-DBH-SAP is freed from the targeted neuron in a meaningful condition. There has never been a reported identification of a targeted toxin, functionally or not, after it has eliminated its targeted neuron. Current evidence indicates that effective suicide transport agents undergo endocytosis at nerve terminals followed by retrograde axonal transport of the endocytic vesicles containing the toxin. Experiments using vincristine have shown that the retrograde axonal transport of suicide transport toxins utilizes the fast transport system (microtubules). However, it is not known what determines whether or not a specific toxin-ligand undergoes axonal transport after internalization.