INT99750

Context Info Confidence 0.73 First Reported 2001 Last Reported 2007 Negated 0 Speculated 1 Reported most in Body Documents 2 Total Number 13 Disease Relevance 1.28 Pain Relevance 0.63

cytoskeletal protein binding (Gphn) plasma membrane (Gphn) cytoskeleton (Gphn) intracellular (Gphn) cytoplasm (Gphn)

Anatomy Link Frequency neurons 2 pore 2 nucleus 2 spinal cord 1 synapses 1 Gphn (Mus musculus)

Pain Link Frequency Relevance Heat Spinal cord 26 99.32 Action potential 1 96.20 GABAergic 1 90.40 tetrodotoxin 14 84.72 antagonist 86 82.28 gABA 5 75.00 Glutamate 1 64.48 Neuronal excitability 2 52.00 agonist 2 43.28 Glutamate receptor 25 39.28

Disease Link Frequency Relevance Heat Targeted Disruption 84 98.68 Disease 12 96.84 Neurologic Manifestations 12 90.40 Death 12 83.36 Sprains And Strains 36 5.00

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Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

Further evidence for functional synaptic activity was provided by the detection of co-localization of gephyrin and synaptophysin at 5 DIV using confocal microscopy.

Localization (co-localization) of gephyrin

1) Confidence 0.73 Published 2001 Journal Neuroscience Section Abstract Doc Link 11738262 Disease Relevance 0 Pain Relevance 0.46

Interestingly, in the NLS-tagged format to divert intrabodies localization, they were able to promote a partial relocalization of gephyrin aggregates into the nucleus.

Spec (partial) Localization (relocalization) of gephyrin in nucleus

2) Confidence 0.65 Published 2007 Journal J Mol Neurosci Section Body Doc Link PMC2758390 Disease Relevance 0.11 Pain Relevance 0

We believe that the lack of a massive translocation of gephyrin aggregates into the nucleus is probably caused by their size—too big to allow nuclear pore crossing.

Localization (translocation) of gephyrin in pore

3) Confidence 0.65 Published 2007 Journal J Mol Neurosci Section Body Doc Link PMC2758390 Disease Relevance 0.05 Pain Relevance 0

Interestingly, in the NLS-tagged format to divert intrabodies localization, they were able to promote a partial relocalization of gephyrin aggregates into the nucleus.

Localization (aggregates) of gephyrin in nucleus

4) Confidence 0.57 Published 2007 Journal J Mol Neurosci Section Body Doc Link PMC2758390 Disease Relevance 0.11 Pain Relevance 0

We believe that the lack of a massive translocation of gephyrin aggregates into the nucleus is probably caused by their size—too big to allow nuclear pore crossing.

Localization (aggregates) of gephyrin in pore

5) Confidence 0.57 Published 2007 Journal J Mol Neurosci Section Body Doc Link PMC2758390 Disease Relevance 0.05 Pain Relevance 0

When gephyrin-EGFP and individual intrabodies were co-transfected, a massive fraction of scFvGeph-2/scFvGeph-9 was relocalized to gephyrin intracytoplasmic aggregates, thus resulting in colocalization of the two proteins (Fig. 2a).

Localization (relocalized) of gephyrin

6) Confidence 0.57 Published 2007 Journal J Mol Neurosci Section Body Doc Link PMC2758390 Disease Relevance 0 Pain Relevance 0

Gephyrin KO mice have been extremely useful for unveiling several aspects of gephyrin-mediated receptor localization at central synapses (Feng et al. 1998).

Localization (localization) of gephyrin-mediated in synapses associated with targeted disruption

7) Confidence 0.57 Published 2007 Journal J Mol Neurosci Section Body Doc Link PMC2758390 Disease Relevance 0.52 Pain Relevance 0.08

The critical contribution of gephyrin to the postsynaptic localization of GlyRs in the spinal cord has been elegantly demonstrated by gene ablation experiments (Feng et al. 1998).

Localization (localization) of gephyrin in spinal cord associated with spinal cord

8) Confidence 0.53 Published 2007 Journal J Mol Neurosci Section Body Doc Link PMC2758390 Disease Relevance 0.33 Pain Relevance 0.08

Twenty-four hours after transfection, immunocytochemical experiments revealed that not only gephyrin was efficiently removed from most subsynaptic sites (Fig. 3a), but also that the number of GlyR clusters were dramatically reduced (Fig. 3b) compared to neurons transfected with EGFP alone.

Localization (removed) of gephyrin in neurons

9) Confidence 0.53 Published 2007 Journal J Mol Neurosci Section Body Doc Link PMC2758390 Disease Relevance 0 Pain Relevance 0

Second, they are specifically relocalized to gephyrin cytoplasmic aggregates.

Localization (relocalized) of gephyrin

10) Confidence 0.53 Published 2007 Journal J Mol Neurosci Section Body Doc Link PMC2758390 Disease Relevance 0.12 Pain Relevance 0

Finally, and most importantly, when ectopically expressed in cultured hippocampal neurons, both selected intrabodies were able to remove endogenous gephyrin from GlyRs clusters, leading to a decreased number of GlyR immunoreactive punctae associated with a severe reduction in the mean amplitude of glycine-evoked currents.

Localization (remove) of gephyrin in neurons

11) Confidence 0.53 Published 2007 Journal J Mol Neurosci Section Body Doc Link PMC2758390 Disease Relevance 0 Pain Relevance 0

When gephyrin-EGFP and individual intrabodies were co-transfected, a massive fraction of scFvGeph-2/scFvGeph-9 was relocalized to gephyrin intracytoplasmic aggregates, thus resulting in colocalization of the two proteins (Fig. 2a).

Localization (relocalized) of gephyrin

12) Confidence 0.50 Published 2007 Journal J Mol Neurosci Section Body Doc Link PMC2758390 Disease Relevance 0 Pain Relevance 0

Note that the nuclear accumulation of scFv-Gephyrin-NLS was associated with a marked reduction of both gephyrin (scFv + Gephyrin in A) and glycine receptor clusters (scFv + GlyRs in B).

Localization (accumulation) of scFv-Gephyrin-NLS

13) Confidence 0.50 Published 2007 Journal J Mol Neurosci Section Body Doc Link PMC2758390 Disease Relevance 0 Pain Relevance 0

General Comments

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