The Scaffold Protein Homer1b/c Links Metabotropic Glutamate Receptor 5 to Extracellular Signal-Regulated Protein Kinase Cascades in Neurons

• DOI: 10.1523/jneurosci.4360-04.2005
• Publication Date: 2005-03-10T01:59:20Z
• Authors: Limin Mao; Lu Yang; Qingsong Tang; Shazia Samdani; Guochi Zhang; John Q. Wang
• Keywords: Neurons; 0303 health sciences; MAP Kinase Signaling System; Corpus Striatum; Rats; 03 medical and health sciences; Homer Scaffolding Proteins; Nuclear Matrix-Associated Proteins; Receptors, Kainic Acid; Animals; Phosphorylation; Carrier Proteins; Extracellular Signal-Regulated MAP Kinases; Excitatory Amino Acid Antagonists; Cells, Cultured

Group I metabotropic glutamate receptors (mGluRs) increase cellular levels of inositol-1,4,5-triphosphate (IP3) and thereby trigger intracellular Ca2+ release. Also, group mGluRs are organized with members Homer scaffold proteins into multiprotein complexes involved in postreceptor signaling. In this study, we investigated the relative importance IP3/Ca2+ signaling novel mGluR-mediated activation extracellular signal-regulated protein kinases 1 2 (ERK1/2) cultured rat striatal neurons. We found that selective mGluR5, but not mGluR1, increased ERK1/2 phosphorylation. Whereas cascade transmits a small portion signals from mGluR5 to ERK1/2, member family Homer1b/c forms central pathway linking Ca2+-independent manner. This was demonstrated by findings mGluR5-mediated phosphorylation mostly reduced cell-permeable Tat-fusion peptide selectively disrupted interaction interfering RNAs knocked down proteins. Furthermore, when only coactivated both IP3/Ca2+- Homer1b/c-dependent pathways, showed ability phosphorylate two transcription factors, Elk-1 cAMP response element-binding protein, facilitated c-Fos expression. Together, have identified coordinated pathways (a conventional vs pathway) differentially mediate mGluR5-ERK coupling Both Ca2+-dependent -independent corequired activate level sufficient achieve mGluR5-dependent synapse-to-nucleus communication imperative for transcriptional regulation.