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Homer1  -  homer homolog 1 (Drosophila)

Mus musculus

Synonyms: Homer protein homolog 1, Homer-1, PSD-Zip45, SYN47, VASP/Ena-related gene up-regulated during seizure and LTP 1, ...
 
 
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Disease relevance of Homer1

  • A cyanobacterial (blue-green algal) bloom containing Microcystis aeruginosa (dominant), M. viridis, and M. wesenbergii, was collected from Homer Lake (Illinois, U.S.A.) in the summer of 1988 and microcystins were isolated [1].
 

High impact information on Homer1

 

Biological context of Homer1

 

Anatomical context of Homer1

  • Distinct roles for different Homer1 isoforms in behaviors and associated prefrontal cortex function [10].
  • Cupidin, an isoform of Homer/Vesl, interacts with the actin cytoskeleton and activated rho family small GTPases and is expressed in developing mouse cerebellar granule cells [11].
  • The data demonstrate that kindling-induced epileptogenesis leads to a striking overexpression of Homer 1A in the hippocampus, which may represent an intrinsic antiepileptogenic and anticonvulsant mechanism in the course of epileptogenesis that counteracts progression of the disease [7].
  • We report here on the relative sub-cellular localisation of InsP(3)Rs and Homer proteins in skeletal muscle cells with respect to the localisation of RyRs [12].
  • Consistent herewith, in sub-cellular fractionation experiments, Homer proteins and InsP(3)R were both found in the fractions enriched in longitudinal sarcoplasmic reticulum (LSR) but not in fractions of terminal cisternae that are enriched in RyRs [12].
 

Associations of Homer1 with chemical compounds

  • PFC overexpression of the IEG Homer1 isoform Homer1a reversed the genotypic differences in behavioral adaptation to repeated stress, whereas overexpression of the constitutively expressed Homer1 isoform Homer1c reversed the genotypic differences in sensorimotor and cognitive processing, as well as cocaine behavioral sensitivity [10].
  • Thus, in skeletal muscle, Homer proteins may play a role in the organisation of a second Ca(2+) signalling compartment containing the InsP(3)R, but are apparently not involved in the organisation of RyRs at triads [12].
  • Rapid redistribution of the postsynaptic density protein PSD-Zip45 (Homer 1c) and its differential regulation by NMDA receptors and calcium channels [13].
  • Actinomycin D and cycloheximide experiments have revealed that, despite the presence of the mRNA-destabilizing AU-rich motif, transcriptional activation is a main determinant for selective Homer 1a mRNA induction [14].
 

Regulatory relationships of Homer1

  • Three Homer genes regulate the activity of metabotropic glutamate receptors mGluR1a and mGluR5 and their coupling to releasable intracellular Ca2+ pools and ion channels [8].
 

Other interactions of Homer1

 

Analytical, diagnostic and therapeutic context of Homer1

  • Here, we report that Homer1-knockout (Homer1-KO) mice exhibit behavioral and neurochemical abnormalities that are consistent with the animal models of schizophrenia [16].
  • The overexpression of Homer 1A in the hippocampus of kindled rats was confirmed by RT-PCR [7].
  • Immunofluorescence analysis showed that both Homer and InsP(3)R proteins present a staining pattern indicative of a localisation at the Z-line, clearly distinct from that of RyR1 [12].
  • Moreover, fluorescent in situ hybridization documented that new primary Homer 1 transcripts are induced in neuronal nuclei within a few minutes after seizure, typical of IEGs, and that Homer 1b-specific exons are excluded from the activity-induced transcripts [8].
  • We investigated the mechanism underlying Homer 1a mRNA induction in cerebellar granule cell culture [14].

References

  1. Structural modifications imparting reduced toxicity in microcystins from Microcystis spp. Stotts, R.R., Namikoshi, M., Haschek, W.M., Rinehart, K.L., Carmichael, W.W., Dahlem, A.M., Beasley, V.R. Toxicon (1993) [Pubmed]
  2. Molecular morphogens for dendritic spines. Ehlers, M.D. Trends Neurosci. (2002) [Pubmed]
  3. Homer proteins regulate sensitivity to cocaine. Szumlinski, K.K., Dehoff, M.H., Kang, S.H., Frys, K.A., Lominac, K.D., Klugmann, M., Rohrer, J., Griffin, W., Toda, S., Champtiaux, N.P., Berry, T., Tu, J.C., Shealy, S.E., During, M.J., Middaugh, L.D., Worley, P.F., Kalivas, P.W. Neuron (2004) [Pubmed]
  4. Homer 1 Mediates Store- and Inositol 1,4,5-Trisphosphate Receptor-dependent Translocation and Retrieval of TRPC3 to the Plasma Membrane. Kim, J.Y., Zeng, W., Kiselyov, K., Yuan, J.P., Dehoff, M.H., Mikoshiba, K., Worley, P.F., Muallem, S. J. Biol. Chem. (2006) [Pubmed]
  5. An N-terminal sequence specific for a novel Homer1 isoform controls trafficking of group I metabotropic glutamate receptor in mammalian cells. Saito, H., Kimura, M., Inanobe, A., Ohe, T., Kurachi, Y. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
  6. Homer modulates NFAT-dependent signaling during muscle differentiation. Stiber, J.A., Tabatabaei, N., Hawkins, A.F., Hawke, T., Worley, P.F., Williams, R.S., Rosenberg, P. Dev. Biol. (2005) [Pubmed]
  7. Kindling-induced overexpression of Homer 1A and its functional implications for epileptogenesis. Potschka, H., Krupp, E., Ebert, U., Gümbel, C., Leichtlein, C., Lorch, B., Pickert, A., Kramps, S., Young, K., Grüne, U., Keller, A., Welschof, M., Vogt, G., Xiao, B., Worley, P.F., Löscher, W., Hiemisch, H. Eur. J. Neurosci. (2002) [Pubmed]
  8. Synaptic activity-induced conversion of intronic to exonic sequence in Homer 1 immediate early gene expression. Bottai, D., Guzowski, J.F., Schwarz, M.K., Kang, S.H., Xiao, B., Lanahan, A., Worley, P.F., Seeburg, P.H. J. Neurosci. (2002) [Pubmed]
  9. Homer2 is necessary for EtOH-induced neuroplasticity. Szumlinski, K.K., Lominac, K.D., Oleson, E.B., Walker, J.K., Mason, A., Dehoff, M.H., Klugmann, M., Klugman, M., Cagle, S., Welt, K., During, M., Worley, P.F., Middaugh, L.D., Kalivas, P.W. J. Neurosci. (2005) [Pubmed]
  10. Distinct roles for different Homer1 isoforms in behaviors and associated prefrontal cortex function. Lominac, K.D., Oleson, E.B., Pava, M., Klugmann, M., Schwarz, M.K., Seeburg, P.H., During, M.J., Worley, P.F., Kalivas, P.W., Szumlinski, K.K. J. Neurosci. (2005) [Pubmed]
  11. Cupidin, an isoform of Homer/Vesl, interacts with the actin cytoskeleton and activated rho family small GTPases and is expressed in developing mouse cerebellar granule cells. Shiraishi, Y., Mizutani, A., Bito, H., Fujisawa, K., Narumiya, S., Mikoshiba, K., Furuichi, T. J. Neurosci. (1999) [Pubmed]
  12. Homer proteins and InsP(3) receptors co-localise in the longitudinal sarcoplasmic reticulum of skeletal muscle fibres. Salanova, M., Priori, G., Barone, V., Intravaia, E., Flucher, B., Ciruela, F., McIlhinney, R.A., Parys, J.B., Mikoshiba, K., Sorrentino, V. Cell Calcium (2002) [Pubmed]
  13. Rapid redistribution of the postsynaptic density protein PSD-Zip45 (Homer 1c) and its differential regulation by NMDA receptors and calcium channels. Okabe, S., Urushido, T., Konno, D., Okado, H., Sobue, K. J. Neurosci. (2001) [Pubmed]
  14. NMDA receptor stimulation and brain-derived neurotrophic factor upregulate homer 1a mRNA via the mitogen-activated protein kinase cascade in cultured cerebellar granule cells. Sato, M., Suzuki, K., Nakanishi, S. J. Neurosci. (2001) [Pubmed]
  15. Differential expression of Homer family proteins in the developing mouse brain. Shiraishi, Y., Mizutani, A., Yuasa, S., Mikoshiba, K., Furuichi, T. J. Comp. Neurol. (2004) [Pubmed]
  16. Behavioral and neurochemical phenotyping of Homer1 mutant mice: possible relevance to schizophrenia. Szumlinski, K.K., Lominac, K.D., Kleschen, M.J., Oleson, E.B., Dehoff, M.H., Schwarz, M.K., Schwartz, M.K., Seeburg, P.H., Seeberg, P.H., Worley, P.F., Kalivas, P.W. Genes Brain Behav. (2005) [Pubmed]
 
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