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Brain Slice Biotinylation: An Ex Vivo Approach to Measure Region-specific Plasma Membrane Protein Trafficking in Adult Neurons
Published on: April 3, 2014
Mechanism underlying activity-dependent insertion of TrkB into the neuronal surface
Ling Zhao1, Ai-Li Sheng, Shu-Hong Huang
1Department of Neurobiology, Key Laboratory of Medical Neurobiology, School of Medicine, Shandong University, Shandong, P.R. China.
Journal of Cell Science
|August 13, 2009
Summary
Brain-derived neurotrophic factor (BDNF) preferentially affects active neurons through TrkB receptor insertion. This study reveals Cdk5-mediated phosphorylation is key for TrkB surface delivery, enhancing synaptic plasticity.
Area of Science:
- Neuroscience
- Cell Biology
- Molecular Biology
Background:
- Brain-derived neurotrophic factor (BDNF) signaling is crucial for neuronal function.
- Activity-dependent TrkB receptor insertion into the plasma membrane influences BDNF's effect on active neurons.
- The precise mechanisms governing TrkB receptor surface recruitment remain incompletely understood.
Purpose of the Study:
- To investigate the cellular and molecular mechanisms of TrkB receptor recruitment to the plasma membrane.
- To elucidate the role of neuronal activity, specifically chemical long-term potentiation (cLTP), in TrkB surface delivery.
- To identify key molecular players involved in activity-dependent TrkB surface insertion.
Main Methods:
- Development of a fluorescence ratiometric assay to quantify surface TrkB receptors.
- Induction of chemical long-term potentiation (cLTP) in hippocampal neurons.
- Mutagenesis studies of the TrkB receptor and analysis of phosphorylation events.
Main Results:
- cLTP-induced TrkB surface recruitment occurs rapidly (t(1/2) ~2.3 min) on neurites and requires an intact cytoskeleton.
- The juxtamembrane domain of TrkB is essential and sufficient for activity-dependent plasma membrane insertion.
- Phosphorylation of TrkB at Ser478 by cyclin-dependent kinase 5 (Cdk5) is critical for cLTP-induced surface insertion.
- TrkB surface recruitment is enhanced in postsynaptic regions, potentially increasing sensitivity to BDNF.
Conclusions:
- Neuronal activity drives rapid, cytoskeleton-dependent insertion of TrkB receptors to the neuronal surface.
- Cdk5-mediated phosphorylation at Ser478 is a key regulatory step for TrkB surface delivery.
- This activity-dependent TrkB surface recruitment mechanism enhances postsynaptic sensitivity to BDNF, contributing to synaptic plasticity.
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