(+)-MCPG induces PKCepsilon translocation in cortical synaptosomes through a PLD-coupled mGluR

Area of Science:

• Neuroscience
• Molecular Biology
• Biochemistry

Background:

• Metabotropic glutamate receptors (mGluRs) are crucial for synaptic transmission and plasticity.
• Protein kinase C (PKC) isozymes play vital roles in neuronal signaling and function.
• Understanding how mGluRs regulate PKC isozymes is key to deciphering neuronal communication.

Purpose of the Study:

• To investigate whether distinct mGluR agonists can induce the translocation of specific PKC isozymes in nerve terminals.
• To identify the mGluR subtypes and associated signaling pathways involved in PKC translocation.
• To elucidate the role of phospholipase D (PLD) in mGluR-mediated PKC signaling.

Main Methods:

• Utilized rat cortical synaptosomes for biochemical assays.
• Administered specific mGluR agonists and antagonists, including 1S,3R-ACPD and (+)-MCPG.
• Measured the translocation of Ca++-independent PKCepsilon and Ca++-dependent PKCbeta.
• Assessed phospholipase D activity via [3H]phosphoethanol production.

Main Results:

• 1S,3R-ACPD induced significant translocation of Ca++-independent PKCepsilon, but not PKCbeta.
• (+)-MCPG also induced PKCepsilon translocation, distinct from 1S,3R-ACPD's effect.
• A novel mGluR antagonist targeting phospholipase D-coupled receptors inhibited (+)-MCPG-induced PKCepsilon translocation.
• (+)-MCPG directly stimulated phospholipase D activity in synaptosomes.

Conclusions:

• Cortical nerve terminals express distinct mGluRs coupled to different signal transduction pathways.
• (+)-MCPG triggers PKCepsilon translocation, potentially via an mGluR linked to phospholipase D.
• This mGluR-PLD pathway influences PKC translocation in a calcium-independent manner, highlighting novel signaling mechanisms in neurons.