title: Homer binds a novel proline-rich motif and links group 1 metabotropic glutamate receptors with IP3 receptors.
abstract: Group I 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.
authors.affiliation: Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: J C
authors.initials: JC
authors.lastname: Tu
authors.forename: B
authors.initials: B
authors.lastname: Xiao
authors.forename: J P
authors.initials: JP
authors.lastname: Yuan
authors.forename: A A
authors.initials: AA
authors.lastname: Lanahan
authors.forename: K
authors.initials: K
authors.lastname: Leoffert
authors.forename: M
authors.initials: M
authors.lastname: Li
authors.forename: D J
authors.initials: DJ
authors.lastname: Linden
authors.forename: P F
authors.initials: PF
authors.lastname: Worley
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D034281:Dynamins; D020558:GTP Phosphohydrolases / Q000235:genetics; D015870:Gene Expression; D017781:Genes, Immediate-Early; D018698:Glutamic Acid / Q000494:pharmacology; D000072233:Homer Scaffolding Proteins; D053496:Inositol 1,4,5-Trisphosphate Receptors; D007425:Intracellular Membranes / Q000378:metabolism; D008024:Ligands; D008969:Molecular Sequence Data; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D011392:Proline / Q000235:genetics*; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013997:Time Factors
chemical_list: D015220:Calcium Channels; D002352:Carrier Proteins; D000072233:Homer Scaffolding Proteins; D053496:Inositol 1,4,5-Trisphosphate Receptors; D008024:Ligands; D009479:Neuropeptides; D018160:Receptors, Cytoplasmic and Nuclear; D018094:Receptors, Metabotropic Glutamate; D018698:Glutamic Acid; D011392:Proline; D020558:GTP Phosphohydrolases; D034281:Dynamins; D002118:Calcium