Carboxypeptidase E Regulates Activity-Dependent TrkB Neuronal Surface Insertion and Hippocampal Memory.

Area of Science:

• Neuroscience
• Molecular Biology
• Cell Biology

Background:

• Brain-derived neurotrophic factor (BDNF) preferentially affects active neurons, but the molecular mechanisms are unclear.
• Activity-dependent insertion of the Tropomyosin-related kinase B (TrkB) receptor into the plasma membrane is implicated but poorly understood.

Purpose of the Study:

• To investigate the role of Carboxypeptidase E (CPE) in regulating TrkB surface delivery and BDNF signaling.
• To elucidate the molecular mechanisms underlying activity-dependent TrkB trafficking in hippocampal neurons.

Main Methods:

• Utilized total internal reflection fluorescence and line plot assays to track TrkB transport.
• Employed TAT-CPE^452-466 peptide to block CPE-TrkB interaction in cultured neurons and mouse models.
• Assessed TrkB phosphorylation and fear conditioning in response to experimental manipulation.

Main Results:

• CPE facilitates TrkB transport to the plasma membrane in response to neuronal activity.
• Specific domains in TrkB (Box2) and CPE (C-terminus) are crucial for activity-dependent TrkB insertion.
• Blocking CPE-TrkB interaction inhibited BDNF signaling, synaptic plasticity, and fear memory acquisition/consolidation.

Conclusions:

• CPE plays a novel role in modulating activity-induced TrkB surface insertion.
• CPE is essential for TrkB-dependent synaptic plasticity and hippocampal memory formation.
• Findings offer insights into CPE's function in TrkB intracellular trafficking and memory modulation.