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Activation of mGluR5 Induces Rapid and Long-Lasting Protein Kinase D Phosphorylation in Hippocampal Neurons

Abstract

Metabotropic glutamate receptors (mGluRs), including mGluR5, play a central role in regulating the strength and plasticity of synaptic connections in the brain. However, the signaling pathways that connect mGluRs to their downstream effectors are not yet fully understood. Here, we report that stimulation of mGluR5 in hippocampal cultures and slices results in phosphorylation of protein kinase D (PKD) at the autophosphorylation site Ser-916. This phosphorylation event occurs within 30 s of stimulation, persists for at least 24 h, and is dependent on activation of phospholipase C and protein kinase C. Our data suggest that activation of PKD may represent a novel signaling pathway linking mGluR5 to its downstream targets. These findings have important implications for the study of the molecular mechanisms underlying mGluR-dependent synaptic plasticity.

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Abbreviations

ACSF:

Artificial cerebrospinal fluid

ANOVA:

Analysis of variance

DAG:

Diacylglycerol

DHPG:

3,5-Dihydroxyphenylglycine

mGluR:

Metabotropic glutamate receptor

PKC:

Protein kinase C

PKD:

Protein kinase D

PLC:

Phospholipase C

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Acknowledgments

We would like to thank Kathleen Oram, Zachary Cohen, Erik Sklar, and Suzanne Meagher for excellent technical and administrative assistance. This work was supported by grants from HHMI, FRAXA, NIMH, NICHD, and the Simons Foundation.

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Correspondence to Mark F. Bear.

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Krueger, D.D., Osterweil, E.K. & Bear, M.F. Activation of mGluR5 Induces Rapid and Long-Lasting Protein Kinase D Phosphorylation in Hippocampal Neurons. J Mol Neurosci 42, 1–8 (2010). https://doi.org/10.1007/s12031-010-9338-9

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  • DOI: https://doi.org/10.1007/s12031-010-9338-9

Keywords

  • mGluR5
  • Protein kinase D
  • DHPG
  • MPEP
  • Hippocampus
  • Primary culture