Endogenous homer proteins regulate metabotropic glutamate receptor signaling in neurons.

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Paul J Kammermeier

Abstract

Group I metabotropic glutamate receptors (mGluR1 and mGluR5) are important neuronal mediators of postsynaptic signaling that influence synaptic strength, plasticity, and other factors. Regulation of group I mGluR localization and function by Homer proteins appears to be a viable means for neurons to fine-tune these processes. The presence of different Homer isoforms can act as a switch to reprioritize mGluR1 and mGluR5 signaling at the point of IP(3) receptor activation by promoting or reducing activation of specific downstream effectors. Furthermore, these Homer-dependent effects on mGluR signaling may mechanistically underlie many of the long-term changes in neuronal function associated with changes in Homer protein expression described in the recent literature. However, most studies focusing on mGluR regulation by Homer proteins used relatively long-term overexpression. Thus, a definitive demonstration of mGluR1/5 signal regulation by natively expressed Homer proteins has been elusive. I examined the ability of endogenous Homer 1a to alter mGluR signaling in rat sympathetic neurons and hippocampal autapses using pituitary adenylate cyclase activating peptide (PACAP) to induce native Homer 1a expression. In sympathetic neuron...Continue Reading

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