RT Journal Article SR Electronic T1 Dendritic and Axonal Targeting of Type 5 Metabotropic Glutamate Receptor Is Regulated by Homer1 Proteins and Neuronal Excitation JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 8710 OP 8716 DO 10.1523/JNEUROSCI.20-23-08710.2000 VO 20 IS 23 A1 Fabrice Ango A1 Jean-Philippe Pin A1 Jian Chen Tu A1 Bo Xiao A1 Paul F. Worley A1 Joel Bockaert A1 Laurent Fagni YR 2000 UL http://www.jneurosci.org/content/20/23/8710.abstract AB The physiological actions of neurotransmitter receptors are intimately linked to their proper neuronal compartment localization. Here we studied the effect of the metabotropic glutamate receptor (mGluR)-interacting proteins, Homer1a, b, and c, in the targeting of mGluR5 in neurons. We found that mGluR5 was exclusively localized in cell bodies when transfected alone in cultured cerebellar granule cells. In contrast, mGluR5 was found also in dendrites when coexpressed with Homer1b or Homer1c, and in both dendrites and axons when cotransfected with Homer1a. In dendrites, cotransfected mGluR5 and Homer1b/c formed clusters that colocalized with the synaptic marker synaptophysin. Interestingly when transfected alone, the Homer proteins were also translocated to neurites but did not form such clusters. Depolarization of the neurons with a mixture of ionotropic glutamate receptor agonists, NMDA and kainate, or potassium channel blockers, tetraethylammonium and 4-aminopyridine, induced transient expression of endogenous Homer1a and persistent neuritic localization of transfected mGluR5 even long after degradation of Homer1a. These results suggest that Homer1a/b/c proteins are involved in the targeting of mGluR5 to dendritic synaptic sites and/or axons and that this effect can be regulated by neuronal activity. Because the activity-dependent effect of endogenous Homer1a was also long-lasting, the axonal targeting of mGluR5 by this protein is likely to play an important role in synaptic plasticity.