Homer Binds a Novel Proline-Rich Motif and Links Group 1 Metabotropic Glutamate Receptors with IP3 Receptors

• Published in: Neuron (Cambridge, Mass.) Vol. 21; no. 4; pp. 717 - 726
• Main Authors: Tu, Jian Cheng, Xiao, Bo, Yuan, Joseph P, Lanahan, Anthony A, Leoffert, Kathleen, Li, Min, Linden, David J, Worley, Paul F
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.10.1998
• Subjects: Amino Acid Sequence; Animals; Calcium - metabolism; Calcium Channels - genetics; Calcium Channels - metabolism; Carrier Proteins - genetics; Carrier Proteins - metabolism; Carrier Proteins - physiology; Dynamins; Gene Expression; Genes, Immediate-Early; Glutamic Acid - pharmacology; GTP Phosphohydrolases - genetics; Homer protein; Homer Scaffolding Proteins; Inositol 1,4,5-Trisphosphate Receptors; Intracellular Membranes - metabolism; Ligands; Molecular Sequence Data; Neuropeptides - genetics; Neuropeptides - metabolism; Neuropeptides - physiology; proline; Proline - genetics; Rats; Receptors, Cytoplasmic and Nuclear - genetics; Receptors, Cytoplasmic and Nuclear - metabolism; Receptors, Metabotropic Glutamate - antagonists & inhibitors; Receptors, Metabotropic Glutamate - metabolism; Time Factors
• ISSN: 0896-6273; 1097-4199
• DOI: 10.1016/S0896-6273(00)80589-9

Group 1 metabotropic glutamate receptors (mGluRs) activate PI turnover and thereby trigger intracellular calcium release. Previously, we demonstrated that mGluRs form natural complexes with members of a family of Homer-related synaptic proteins. Here, we present evidence that Homer proteins form a physical tether linking mGluRs with the inositol trisphosphate receptors (IP3R). A novel proline-rich “Homer ligand” (PPXXFr) is identified in group 1 mGluRs and IP3R, and these receptors coimmunoprecipitate as a complex with Homer from brain. Expression of the IEG form of Homer, which lacks the ability to cross-link, modulates mGluR-induced intracellular calcium release. These studies identify a novel mechanism in calcium signaling and provide evidence that an IEG, whose expression is driven by synaptic activity, can directly modify a specific synaptic function.