title: Homer: a protein that selectively binds metabotropic glutamate receptors.
abstract: Spatial localization and clustering of membrane proteins is critical to neuronal development and synaptic plasticity. Recent studies have identified a family of proteins, the PDZ proteins, that contain modular PDZ domains and interact with synaptic ionotropic glutamate receptors and ion channels. PDZ proteins are thought to have a role in defining the cellular distribution of the proteins that interact with them. Here we report a novel dendritic protein, Homer, that contains a single, PDZ-like domain and binds specifically to the carboxy terminus of phosphoinositide-linked metabotropic glutamate receptors. Homer is highly divergent from known PDZ proteins and seems to represent a novel family. The Homer gene is also distinct from members of the PDZ family in that its expression is regulated as an immediate early gene and is dynamically responsive to physiological synaptic activity, particularly during cortical development. This dynamic transcriptional control suggests that Homer mediates a novel cellular mechanism that regulates metabotropic glutamate signalling.
authors.affiliation: Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: P R
authors.initials: PR
authors.lastname: Brakeman
authors.forename: A A
authors.initials: AA
authors.lastname: Lanahan
authors.forename: R
authors.initials: R
authors.lastname: O'Brien
authors.forename: K
authors.initials: K
authors.lastname: Roche
authors.forename: C A
authors.initials: CA
authors.lastname: Barnes
authors.forename: R L
authors.initials: RL
authors.lastname: Huganir
authors.forename: P F
authors.initials: PF
authors.lastname: Worley
mesh_terms: D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000378:metabolism; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D003001:Cloning, Molecular; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000378:metabolism; D000072233:Homer Scaffolding Proteins; D006801:Humans; D007124:Immunoenzyme Techniques; D051379:Mice; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D009479:Neuropeptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D017384:Sequence Deletion; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D013569:Synapses / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D000072233:Homer Scaffolding Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D012333:RNA, Messenger; D018094:Receptors, Metabotropic Glutamate