SV2 Mediates Entry of Tetanus Neurotoxin into Central Neurons

Tetanus neurotoxin causes the disease tetanus, which is characterized by rigid paralysis. The toxin acts by inhibiting the release of neurotransmitters from inhibitory neurons in the spinal cord that innervate motor neurons and is unique among the clostridial neurotoxins due to its ability to shuttle from the periphery to the central nervous system. Tetanus neurotoxin is thought to interact with a high affinity receptor complex that is composed of lipid and protein components; however, the identity of the protein receptor remains elusive. In the current study, we demonstrate that toxin binding, to dissociated hippocampal and spinal cord neurons, is greatly enhanced by driving synaptic vesicle exocytosis. Moreover, tetanus neurotoxin entry and subsequent cleavage of synaptobrevin II, the substrate for this toxin, was also dependent on synaptic vesicle recycling. Next, we identified the potential synaptic vesicle binding protein for the toxin and found that it corresponded to SV2; tetanus neurotoxin was unable to cleave synaptobrevin II in SV2 knockout neurons. Toxin entry into knockout neurons was rescued by infecting with viruses that express SV2A or SV2B. Tetanus toxin elicited the hyper excitability in dissociated spinal cord neurons - due to preferential loss of inhibitory transmission - that is characteristic of the disease. Surprisingly, in dissociated cortical cultures, low concentrations of the toxin preferentially acted on excitatory neurons. Further examination of the distribution of SV2A and SV2B in both spinal cord and cortical neurons revealed that SV2B is to a large extent localized to excitatory terminals, while SV2A is localized to inhibitory terminals. Therefore, the distinct effects of tetanus toxin on cortical and spinal cord neurons are not due to differential expression of SV2 isoforms. In summary, the findings reported here indicate that SV2A and SV2B mediate binding and entry of tetanus neurotoxin into central neurons

Role of the Peroneal Tendons in the Production of the Deformed Foot with Posterior Tibial Tendon Deficiency

Ten patients were identified with traumatic, complete common peroneal nerve palsy, with no previous foot or ankle surgery or trauma distal to the knee, who had undergone anterior transfer of the posterior tibial tendon to the midfoot. Six of these patients had a transfer to the midfoot and four had a Bridle procedure with tenodesis of half of the posterior tibial tendon to the peroneus longus tendon. Average follow-up was 74.9 months (range, 18–351 months). All patients] feet were compared assessing residual muscle strength, the longitudinal arch, and motion at the ankle, subtalar, and Chopart's joint. Weightbearing lateral X-rays and Harris mat studies were done on both feet. In no case was any valgus hindfoot deformity associated with posterior tibial tendon rupture found. It seems that the pathologic condition associated with a posterior tibial tendon deficient foot will not manifest itself if peroneus brevis function is absent