INT346412

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Context Info
Confidence 0.02
First Reported 2010
Last Reported 2010
Negated 0
Speculated 1
Reported most in Body
Documents 1
Total Number 10
Disease Relevance 0.60
Pain Relevance 0.59

This is a graph with borders and nodes. Maybe there is an Imagemap used so the nodes may be linking to some Pages.

cytoplasm (Tesc, Sv2a) transport (Sv2a) transmembrane transporter activity (Sv2a)
endoplasmic reticulum (Sv2a) plasma membrane (Tesc) nucleus (Tesc)
Anatomy Link Frequency
neurons 6
spinal cord 1
inhibitory interneurons 1
Tesc (Mus musculus)
Sv2a (Mus musculus)
Pain Link Frequency Relevance Heat
Neurotransmitter 40 100.00 Very High Very High Very High
Spinal cord 460 98.72 Very High Very High Very High
Central nervous system 60 64.80 Quite High
tetrodotoxin 140 5.00 Very Low Very Low Very Low
Action potential 50 5.00 Very Low Very Low Very Low
antagonist 30 5.00 Very Low Very Low Very Low
sodium channel 10 5.00 Very Low Very Low Very Low
nMDA receptor antagonist 10 5.00 Very Low Very Low Very Low
gABA 10 5.00 Very Low Very Low Very Low
Glutamate 10 5.00 Very Low Very Low Very Low
Disease Link Frequency Relevance Heat
Paralysis 70 99.16 Very High Very High Very High
Infection 40 82.40 Quite High
Targeted Disruption 60 78.64 Quite High
Injury 20 73.28 Quite High
Toxicity 10 72.44 Quite High
Anaerobic Bacterial Infections 220 50.00 Quite Low
Disease 60 5.00 Very Low Very Low Very Low
Poisoning 20 5.00 Very Low Very Low Very Low
Death 10 5.00 Very Low Very Low Very Low
Autolysis 10 5.00 Very Low Very Low Very Low

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
In addition, the higher affinity of SV2 for TeNT would allow for efficient capture of the toxin once it has dissociated from the MN, thus favoring binding and entry into the upstream inhibitory neuron.
TeNT Binding (affinity) of SV2 in neuron
1) Confidence 0.02 Published 2010 Journal PLoS Pathogens Section Body Doc Link PMC2991259 Disease Relevance 0.05 Pain Relevance 0.03
To further confirm that TeNT associated with SV2, we used HCR/T to see if it could compete with BoNT/E for binding to its native receptor, SV2, on hippocampal neurons.
TeNT Binding (associated) of SV2 in neurons
2) Confidence 0.02 Published 2010 Journal PLoS Pathogens Section Body Doc Link PMC2991259 Disease Relevance 0.07 Pain Relevance 0
These results further demonstrate that SV2 plays a critical role in the binding of TeNT to inhibitory terminals in the spinal cord.
TeNT Binding (binding) of SV2 in spinal cord associated with spinal cord
3) Confidence 0.02 Published 2010 Journal PLoS Pathogens Section Body Doc Link PMC2991259 Disease Relevance 0.15 Pain Relevance 0.17
The finding that SV2A/B double KO neurons exhibit decreased binding and entry of TeNT, in conjunction with the ability of TeNT to compete with BoNT/E, strongly implicates SV2 as the receptor for TeNT.
TeNT Binding (receptor) of SV2 in neurons
4) Confidence 0.02 Published 2010 Journal PLoS Pathogens Section Body Doc Link PMC2991259 Disease Relevance 0 Pain Relevance 0.03
To determine, definitively, whether TeNT relies on SV2 to bind and enter neurons, we took advantage of SV2A/B KO mice [51], [52].
TeNT Binding (bind) of SV2 in neurons
5) Confidence 0.02 Published 2010 Journal PLoS Pathogens Section Body Doc Link PMC2991259 Disease Relevance 0 Pain Relevance 0.17
This raises the question as to how TeNT selectively targets inhibitory interneurons, without affecting MNs; that is, why is the toxin not taken up into SV2-harboring SVs that acidify in MNs, thereby triggering translocation and resulting in flaccid paralysis (note: at extremely high concentrations, TeNT can in fact inhibit neurotransmitter release from MNs, probably via interactions with SV2 [61]).
TeNT Binding (interactions) of SV2 in inhibitory interneurons associated with neurotransmitter and paralysis
6) Confidence 0.02 Published 2010 Journal PLoS Pathogens Section Body Doc Link PMC2991259 Disease Relevance 0.17 Pain Relevance 0.09
Consistent with previous reports, we detected that BoNT/B associated with syt I and BoNT/E with SV2, but surprisingly, we observed that TeNT also strongly associated with SV2 (Figure 4A).
TeNT Binding (associated) of SV2
7) Confidence 0.02 Published 2010 Journal PLoS Pathogens Section Body Doc Link PMC2991259 Disease Relevance 0.07 Pain Relevance 0
Thus, both SV2A and B are important for TeNT to recognize and associate with the surface of central neurons.
TeNT Binding (recognize) of SV2A in neurons
8) Confidence 0.02 Published 2010 Journal PLoS Pathogens Section Body Doc Link PMC2991259 Disease Relevance 0.08 Pain Relevance 0.07
The loss of PSGs might dramatically reduce the affinity of TeNT for the peripheral receptor, relative to SV2, so TeNT can be released from the MN and target inhibitory neurons after transcytosis.
TeNT Spec (might) Binding (affinity) of SV2 in neurons
9) Confidence 0.02 Published 2010 Journal PLoS Pathogens Section Body Doc Link PMC2991259 Disease Relevance 0 Pain Relevance 0.03
As opposed to the previous model, the peripheral receptor, rather than SV2, has a higher affinity for TeNT.
TeNT Binding (affinity) of SV2
10) Confidence 0.02 Published 2010 Journal PLoS Pathogens Section Body Doc Link PMC2991259 Disease Relevance 0 Pain Relevance 0

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