Question

Tetanus, commonly called lockjaw, is the result of a bacterial infection from the bacterium Clostridium tetani. It produces muscle spasms (think lots of co-contraction of muscles that would not normally occur). Once the bacteria has made its way into the body, it is taken up by neurons, ultimately making its way to inhibitory interneurons in the spinal cord that will synapse onto α motor neurons that innervate muscle fibers. Use your knowledge of the stretch reflex to answer the following questions.

a. Once in the synapse, C. tetani produces a toxin that cleaves the proteins that participate in the release of neurotransmitter. This results in a reduction of transmitter release at the synapse. Collectively, what are these proteins called? What is the molecular mechanism for how they work together to promote the release of transmitter at the synapse?

Answer 1

C. Tetani cleaves the integral membrane protein (synaptic proteins) of synaptic vesicles. The bacteria C. Tetani produces a neurotoxin named tetanospasmin which causes violent muscular spasms, trismus (lockjaw) and Facial spasm

Toxin, tetanospasmin is made up of heavy and light chain via a disulfide bridge. The H chain binds to the gangliosides on nerves and thus causes internalization. From here, the toxin starts moving through the axons of nerves to the spinal cord where it invades the inhibitory interneurons and disseminates the CNS.

On the other hand the L chain (metalloprotease), cleaves synaptobrevin in the synaptic vesicles. This synaptobrevin is basically a protein responsible for the release of neurotransmitters.

Release of neurotransmitters by synaptobrevin –

Synaptic proteins namely synaptobrevin/VAMP(vesicle associated membrane protein), syntaxin, and SNAP-25 form tight complex (SNARE complex). VAMP has four functional domains. Its amino-terminal is rich in proline isoform while its central portion has coiled-coil region leading to formation of SNARE complex. This protein is connected to the membrane by a single transmembrane domain followed by intravesicular portion. VAMP -2 causes exocytosis of neurotransmitter and endocytosis of synaptic vesicles. TeNT and BoNT causes protein cleavage and causes proteolysis of SNARE followed by inhibition of neurotransmitter release.