INT243956

Context Info Confidence 0.35 First Reported 2007 Last Reported 2008 Negated 0 Speculated 0 Reported most in Body Documents 3 Total Number 7 Disease Relevance 0.94 Pain Relevance 0.35

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

Anatomy Link Frequency neuronal 1 neurons 1 spinal cord 1 amygdala 1 synapses 1 Gphn (Mus musculus)

Pain Link Frequency Relevance Heat Hippocampus 17 98.56 Spinal cord 12 98.00 amygdala 2 97.28 depression 16 83.12 GABAergic 58 69.60 antagonist 35 41.04 tetrodotoxin 5 35.72 Glutamate receptor 22 32.00 medulla 4 18.32 gABA 56 5.00

Disease Link Frequency Relevance Heat Targeted Disruption 49 99.28 Depression 16 83.12 Death 5 80.72 Anxiety Disorder 8 69.44 Neurologic Manifestations 5 60.80 Disease 7 46.96 Respiratory Failure 2 13.72 Sprains And Strains 15 9.84 Generalized Anxiety Disorder 4 5.00 Stress 4 5.00

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

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).

Negative_regulation (reduction) of gephyrin

1) Confidence 0.35 Published 2007 Journal J Mol Neurosci Section Body Doc Link PMC2758390 Disease Relevance 0 Pain Relevance 0

To exploit the intrabodies-based retargeting scheme for depleting endogenous gephyrin from inhibitory synapses, the linker or intervening region of gephyrin molecule was used for the two-hybrid selection method.

Negative_regulation (depleting) of gephyrin in synapses

2) Confidence 0.35 Published 2007 Journal J Mol Neurosci Section Body Doc Link PMC2758390 Disease Relevance 0.18 Pain Relevance 0

In the present study, a nuclear localization signal (NLS)-targeted intrabody for the removal of endogenous gephyrin from inhibitory receptor clusters in cultured hippocampal neurons has been developed.

Negative_regulation (removal) of gephyrin in neurons

3) Confidence 0.35 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).

Negative_regulation (reduction) of Gephyrin

4) Confidence 0.31 Published 2007 Journal J Mol Neurosci Section Body Doc Link PMC2758390 Disease Relevance 0 Pain Relevance 0

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).

Negative_regulation (contribution) of gephyrin in spinal cord associated with spinal cord

5) Confidence 0.30 Published 2007 Journal J Mol Neurosci Section Body Doc Link PMC2758390 Disease Relevance 0.32 Pain Relevance 0.08

Collybistin knock out mice exhibit a region specific loss of postsynaptic gephyrin and GABAA receptor clusters in the hippocampus and the basolateral amygdala.

Negative_regulation (loss) of gephyrin in amygdala associated with targeted disruption, hippocampus and amygdala

6) Confidence 0.15 Published 2008 Journal Frontiers in Molecular Neuroscience Section Body Doc Link PMC2526003 Disease Relevance 0.25 Pain Relevance 0.17

The synaptic formation of gephyrin and GABAA receptor clusters are mutually dependent on each other: neuronal cultures from gephyrin knock out mice show an extensive loss of alpha2 and gamma2 containing GABAA receptor clusters and vice versa in GABAA receptor gamma2 subunit knock out mice the synaptic gephyrin clusters are absent and the remaining alpha-beta containing receptors are diffusely distributed on the cell surface (Craig et al., 1996; Essrich et al., 1998; Günther et al., 1995).

Negative_regulation (formation) of gephyrin in neuronal associated with targeted disruption

7) Confidence 0.11 Published 2008 Journal Frontiers in Molecular Neuroscience Section Body Doc Link PMC2526003 Disease Relevance 0.19 Pain Relevance 0.10

General Comments

This test has worked.