Homer: a protein that selectively binds metabotropic glutamate receptors

Brakeman, Paul; Lanahan, Anthony A.; O’Brien, Richard; Roche, Katherine W.; Barnes, Carol A.; Huganir, Richard L.; Worley, Paul F.

doi:10.1038/386284a0

Cited by 1,000 publications

(1,046 citation statements)

References 27 publications

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“…The Homer family of proteins is the product of three independent mammalian genes (Homer1-3), one Xenopus gene and one Drosophila gene [102][103][104][105]. In humans, Homer1, Homer2 and Homer3 are localized to chromosomes 5, 15 and 19, respectively [105] and Homer transcripts have been identified in many different tissues including: brain, retina, liver, kidney, spleen, testis, thymus, placenta, intestine, as well as cardiac, skeletal and smooth muscle [105][106][107].…”

Section: Molecular Aspects Of Homer Proteinsmentioning

confidence: 99%

“…In humans, Homer1, Homer2 and Homer3 are localized to chromosomes 5, 15 and 19, respectively [105] and Homer transcripts have been identified in many different tissues including: brain, retina, liver, kidney, spleen, testis, thymus, placenta, intestine, as well as cardiac, skeletal and smooth muscle [105][106][107]. First described in the late 1990's, the original family of Homer proteins consisted of Homer1a/b/c, Homer2a/b and 3 [102][103][104][105]. Since that time, 21 Homer mRNAs have been isolated from rat, mouse and human brain, however the proteins for some of these mRNAs have yet to be detected in mammalian brain tissue [107][108][109].…”

Section: Molecular Aspects Of Homer Proteinsmentioning

confidence: 99%

“…Since that time, 21 Homer mRNAs have been isolated from rat, mouse and human brain, however the proteins for some of these mRNAs have yet to be detected in mammalian brain tissue [107][108][109]. The mammalian genes encoding the Homer family of proteins have open reading frames that spread over 10 exons and can give rise to both constitutively expressed, as well as immediate early gene (IEG) products [102,104,110,111]. Exon 1 encodes the 5′ untranslated region (UTR) and contains the translational initiation codon ATG.…”

Section: Molecular Aspects Of Homer Proteinsmentioning

confidence: 99%

“…The EVH1 domain exhibits a high degree of similarity across Homer isoforms and is essential for Homer interactions with a proline-rich sequence (PPSPF) displayed by proteins regulating drug-induced alterations in neuronal morphology, synaptic architecture, and glutamate receptor signaling/intracellular calcium dynamics. Of particular relevance to drug-induced neuroplasticity [e.g., 20,73,74,[78][79][80][81][82][89][90][91][92][93][94][95][96][97][98][99][100][123][124][125][126][127][128][129][130], these proteins include the mGluR1a and mGluR5 subtypes of Group 1 metabotropic glutamate receptors (mGluRs) [34,102,104,107,[131][132][133][134][135][136][137], the NMDA glutamate receptor scaffolding protein Shank [38,132,138,139], the inositol-1,4,5-triphosphate (IP3) receptor, a down-stream mediator of Group1 mGluR signaling [133,[140]…”

Section: Molecular Aspects Of Homer Proteinsmentioning

confidence: 99%

“…Alternative transcript splicing in regions downstream from exon 5 has been reported for all 3 Homer genes and can result in premature termination of transcription prior to the sequences encoding the CC and leucine zipper motifs [102,105,107,110]. This premature termination of transcription results in truncated or "short" Homer isoforms that lack the motifs necessary to multimerize.…”

Section: Molecular Aspects Of Homer Proteinsmentioning

confidence: 99%

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Homers regulate drug-induced neuroplasticity: Implications for addiction

Szumlinski

Ary

Lominac

2008

Biochemical Pharmacology

118

160

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Drug addiction is a chronic, relapsing disorder, characterized by an uncontrollable motivation to seek and use drugs. Converging clinical and preclinical observations implicate pathologies within the corticolimbic glutamate system in the genetic predisposition to, and the development of, an addicted phenotype. Such observations pose cellular factors regulating glutamate transmission as likely molecular candidates in the etiology of addiction. Members of the Homer family of proteins regulate signal transduction through, and the trafficking of, glutamate receptors, as well as maintain and regulate extracellular glutamate levels in corticolimbic brain regions. This review summarizes the existing data implicating the Homer family of protein in acute behavioral and neurochemical sensitivity to drugs of abuse, the development of drug-induced neuroplasticity, as well as other behavioral and cognitive pathologies associated with an addicted state.

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Section: Molecular Aspects Of Homer Proteinsmentioning

confidence: 99%

Section: Molecular Aspects Of Homer Proteinsmentioning

confidence: 99%

Section: Molecular Aspects Of Homer Proteinsmentioning

confidence: 99%

Section: Molecular Aspects Of Homer Proteinsmentioning

confidence: 99%

Section: Molecular Aspects Of Homer Proteinsmentioning

confidence: 99%

See 3 more Smart Citations

Homers regulate drug-induced neuroplasticity: Implications for addiction

Szumlinski

Ary

Lominac

2008

Biochemical Pharmacology

118

160

View full text Add to dashboard Cite

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Immunocytochemical localization of the mGluR1b metabotropic glutamate receptor in the rat hypothalamus

et al. 1998

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The mGluR1 metabotropic glutamate receptor is a G-protein-coupled receptor that exists as different C-terminal splice variants. When expressed in mammalian cells, the mGluR1 splice variants exhibit diverse transduction mechanisms and also slightly differ in their apparent agonist affinities. In the present study, we used an affinity-purified antiserum, specifically reactive to the mGluRlb splice variant, in combination with a highly sensitive preembedding immunocytochemical method for light microscopy to investigate the distribution of this receptor in the rat hypothalamus. An intense immunoreactivity for mGluRlb was observed in distinct hypothalamic nuclei. Thus, neuronal cell bodies and dendrites were stained in the preoptic area, suprachiasmatic nucleus, dorsal hypothalamus, lateral hypothalamus, dorsomedial nucleus, tuberomammilary nucleus, and lateral mammilary body. The ventromedial nucleus exhibited neuropil immunostaining but neuronal cell bodies were not labeled. Strong mGluRlb immunoreactivity was observed in magnocellular neurons of the neuroendocrine supraoptic, paraventricular, and arcuate nuclei. Also, neuronal cell bodies were heavily labeled in the retrochiasmatic nucleus, anterior commissural nucleus, and periventricular nucleus. These immunocytochemical observations, together with previous studies, suggest that mGluRlb is coexpressed with other class I mGluRs in some nuclei throughout the hypothalamus. However, mGluRlb is so far the only receptor of this class strongly expressed in the supraoptic, paraventricular, and arcuate nuclei, which might have relevant implications in the physiological control of the neuroendocrine hypothalamic-pituitary system.

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Immunohistochemical localization of the mGluR1? metabotropic glutamate receptor in the adult rodent forebrain: Evidence for a differential distribution of mGluR1 splice variants

Ferraguti¹,

Conquet²,

Corti³

et al. 1998

J. Comp. Neurol.

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Alternative splicing has been shown to occur at the metabotropic glutamate receptor 1 (mGluR1) gene. Three main isoforms that differ in their carboxy-termini have been described so far and named mGluR1alpha, mGluR1beta and mGluR1c. These variants when expressed in recombinant systems all activate phospholipase C, although the [Ca2+] signals generated have different kinetics. Tissue distribution studies of specific mGluR1 splice variants are limited to the mGluR1alpha isoform. In the present work, we examined the localization of mGluR1beta in the adult rat and mouse forebrain by using a specific antipeptide antibody. Furthermore, the mGluR1beta immunostaining was compared with that obtained with antibodies specific for mGluR1alpha or with a pan-mGluR1 antibody which recognizes all isoforms. mGluR1beta-like immunoreactivity (LI) was found confined to the neuropil and neuronal perikarya and appeared discretely distributed in the rodent forebrain. Differential cellular distribution between mGluR1alpha and mGluR1beta was observed. In the hippocampus, mGluR1alpha-LI was restricted to non-principal neurons in all fields, whereas mGluR1beta-LI was strongest in principal cells of the CA3 field and dentate granule cells but absent in CA1. We have also shown that the vast majority of neurons in the striatum express mGluR1. The predominant form appeared to be mGluR1beta, with a distribution pattern reflecting the patch-matrix organization of the striatum. The specificity of the immunoreactivity described for mGluR1 splice variants was confirmed in mGluR1-deficient mice. The observation of a different cellular and regional distribution of mGluR1 splice variants, in particular in the hippocampus, suggests that they may mediate different roles in synaptic transmission.

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Homer: a protein that selectively binds metabotropic glutamate receptors

Cited by 1,000 publications

References 27 publications

Homers regulate drug-induced neuroplasticity: Implications for addiction

Homers regulate drug-induced neuroplasticity: Implications for addiction

Immunocytochemical localization of the mGluR1b metabotropic glutamate receptor in the rat hypothalamus

Immunohistochemical localization of the mGluR1? metabotropic glutamate receptor in the adult rodent forebrain: Evidence for a differential distribution of mGluR1 splice variants

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