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Updated: Mar 28, 2026
08:47
Monitoring eIF4F Assembly by Measuring eIF4E-eIF4G Interaction in Live Cells
Published on: May 1, 2020
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Translational control of nociception via 4E-binding protein 1
Arkady Khoutorsky1,2, Robert P Bonin3, Robert E Sorge4,5
1Department of Biochemistry, McGill University, Montréal, Canada.
Elife
|December 19, 2015
Summary
Mechanistic/mammalian target of rapamycin (mTOR) activation enhances pain by increasing protein translation. Deleting 4E-binding protein 1 (4E-BP1) reverses mechanical pain hypersensitivity by reducing neuroligin 1 expression and synaptic activity.
Area of Science:
- Neuroscience
- Molecular Biology
- Pain Research
Background:
- Mechanistic/mammalian target of rapamycin (mTOR) kinase pathway activation is linked to pain hypersensitivity.
- The precise molecular mechanisms by which mTOR influences nociception are not fully understood.
Purpose of the Study:
- To investigate the role of eukaryotic initiation factor 4E-binding protein 1 (4E-BP1), an mTOR effector, in pain regulation.
- To elucidate the molecular pathways connecting mTOR signaling to spinal cord synaptic function and pain.
Main Methods:
- Utilized knockout mice lacking 4E-BP1 to assess pain responses.
- Examined spinal cord expression of neuroligin 1 and synaptic activity.
- Employed pharmacological inhibition of eIF4E and genetic reduction of neuroligin 1.
Main Results:
- Mice lacking 4E-BP1 displayed mechanical, but not thermal, pain hypersensitivity.
- Absence of 4E-BP1 led to increased spinal cord neuroligin 1 expression and enhanced excitatory synaptic input.
- Inhibition of eIF4E or reduction of neuroligin 1 normalized synaptic activity and reversed mechanical hypersensitivity.
Conclusions:
- Translational control mediated by 4E-BP1, downstream of mTOR, regulates neuroligin 1 expression in the spinal cord.
- This pathway significantly contributes to enhanced mechanical pain sensitivity by modulating excitatory synaptic transmission.
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