Mechanism of Action of Presynaptic Neurotoxins
Annual rept. Sep 1984-Aug 1985
MARYLAND UNIV BALTIMORE SCHOOL OF MEDICINE
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A cell line of neural origin, N18 RE105 that binds tetanus toxin in a manner identical to that found in normal brain tissue has been identified. Analysis of the ganglioside content of these cells reveals that it has the same composition as brain. These cells were found to internalize tetanus toxin very rapidly at 37 C. The rapid internalization was found to be dependent on temperature and ATP within the cell. Therefore this cell line has provided a valuable model system to characterize tetanus toxin interactions and internalization by brain cells. However, these cells do not release neurotransmitter and therefore functional responses cannot be measured. We have found that another cell line that does have a neurotransmitter release system, the PC12 cells does bind tetanus toxin with high affinity as well. Differentiation of these cells with nerve growth factor leads to an five fold increase in tetanus toxin receptors on these cells. Studies are now underway using this cell line in order to correlate binding, internalization, and biochemical responses of cell with inhibition of neurotransmitter release.