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Gene Review

Homer1  -  homer homolog 1 (Drosophila)

Rattus norvegicus

Synonyms: HOMER1F, Homer, Homer protein homolog 1, PSD-Zip45, VASP/Ena-related gene up-regulated during seizure and LTP 1, ...
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Disease relevance of Homer1


Psychiatry related information on Homer1

  • Signaling through group I mGluRs is regulated, in part, by Homer proteins, and it was found that the blunting of group I mGluR-induced glutamate release and motor activity after repeated cocaine was associated with a reduction in Homer1b/c protein that was selective for the medial nucleus accumbens [5].

High impact information on Homer1

  • This dynamic transcriptional control suggests that Homer mediates a novel cellular mechanism that regulates metabotropic glutamate signalling [6].
  • 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 [6].
  • 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 [6].
  • PI3 kinase enhancer-Homer complex couples mGluRI to PI3 kinase, preventing neuronal apoptosis [7].
  • We demonstrate physiologic binding of PIKE-L to Homer, an adaptor protein known to link metabotropic glutamate receptors to multiple intracellular targets including the inositol 1,4,5-trisphosphate receptor (IP3R) [7].

Biological context of Homer1


Anatomical context of Homer1


Associations of Homer1 with chemical compounds

  • The postsynaptic scaffold proteins ProSAP1/Shank2 and Homer1 are associated with glutamate receptor complexes at rat retinal synapses [16].
  • Actin depolymerization by latrunculin A reduced the synaptic localization of PSD-Zip45, shank, and F-actin but not of PSD-95 or GKAP [17].
  • These data indicate that the expression of behavioural sensitization arises in part from a reduction in Homer1 gene products in the accumbens, while the development of sensitization requires stimulation of AMPA/kainate receptors [11].
  • Structure of the Homer EVH1 domain-peptide complex reveals a new twist in polyproline recognition [18].
  • Here, we present evidence that Homer proteins form a physical tether linking mGluRs with the inositol trisphosphate receptors (IP3R) [19].

Physical interactions of Homer1

  • We have determined the crystal structure of the Homer EVH1 domain complexed with a peptide from mGluR (TPPSPF) [18].

Regulatory relationships of Homer1


Other interactions of Homer1

  • Dynamin 3 is a component of the postsynapse, where it interacts with mGluR5 and Homer [8].
  • Here we report additional members of the Vesl/Homer family of proteins, Vesl-1L and Vesl-2 [25].
  • The double-labeling experiments revealed a high rate of colocalization of ProSAP1/Shank2 with Homer1 and PSD-95, and little colocalization with GRIP [16].
  • In this study we examined whether the expression and loss of behavioral signs of neuropathic pain were associated with changes in the content of the scaffolding proteins Homer and Shank in the post-synaptic density (PSD) of the spinal dorsal horn [26].
  • The EVH1 domain and extreme C-terminal leucine zipper motif of PSD-Zip45 were also critical for these events [17].

Analytical, diagnostic and therapeutic context of Homer1


  1. AAV-mediated hippocampal expression of short and long Homer 1 proteins differentially affect cognition and seizure activity in adult rats. Klugmann, M., Wymond Symes, C., Leichtlein, C.B., Klaussner, B.K., Dunning, J., Fong, D., Young, D., During, M.J. Mol. Cell. Neurosci. (2005) [Pubmed]
  2. Estrogen protects the inner retina from apoptosis and ischemia-induced loss of Vesl-1L/Homer 1c immunoreactive synaptic connections. Kaja, S., Yang, S.H., Wei, J., Fujitani, K., Liu, R., Brun-Zinkernagel, A.M., Simpkins, J.W., Inokuchi, K., Koulen, P. Invest. Ophthalmol. Vis. Sci. (2003) [Pubmed]
  3. Elucidation of Homer 1a function in the nucleus accumbens using adenovirus gene transfer technology. Bowers, M.S., Lake, R.W., Rubinchik, S., Dong, J.Y., Kalivas, P.W. Ann. N. Y. Acad. Sci. (2003) [Pubmed]
  4. Potential role of Homer-2a on cutaneous vascular anomaly. Kim, J.T., Park, S.H., Kim, S.K., Kwon, E.Y., Do, M.H., Hwang, T.H. J. Korean Med. Sci. (2002) [Pubmed]
  5. Repeated cocaine administration attenuates group I metabotropic glutamate receptor-mediated glutamate release and behavioral activation: a potential role for Homer. Swanson, C.J., Baker, D.A., Carson, D., Worley, P.F., Kalivas, P.W. J. Neurosci. (2001) [Pubmed]
  6. Homer: a protein that selectively binds metabotropic glutamate receptors. Brakeman, P.R., Lanahan, A.A., O'Brien, R., Roche, K., Barnes, C.A., Huganir, R.L., Worley, P.F. Nature (1997) [Pubmed]
  7. PI3 kinase enhancer-Homer complex couples mGluRI to PI3 kinase, preventing neuronal apoptosis. Rong, R., Ahn, J.Y., Huang, H., Nagata, E., Kalman, D., Kapp, J.A., Tu, J., Worley, P.F., Snyder, S.H., Ye, K. Nat. Neurosci. (2003) [Pubmed]
  8. Dynamin 3 is a component of the postsynapse, where it interacts with mGluR5 and Homer. Gray, N.W., Fourgeaud, L., Huang, B., Chen, J., Cao, H., Oswald, B.J., Hémar, A., McNiven, M.A. Curr. Biol. (2003) [Pubmed]
  9. Vesl/Homer proteins regulate ryanodine receptor type 2 function and intracellular calcium signaling. Westhoff, J.H., Hwang, S.Y., Duncan, R.S., Ozawa, F., Volpe, P., Inokuchi, K., Koulen, P. Cell Calcium (2003) [Pubmed]
  10. Comprehensive regional and temporal gene expression profiling of the rat brain during the first 24 h after experimental stroke identifies dynamic ischemia-induced gene expression patterns, and reveals a biphasic activation of genes in surviving tissue. Rickhag, M., Wieloch, T., Gidö, G., Elmér, E., Krogh, M., Murray, J., Lohr, S., Bitter, H., Chin, D.J., von Schack, D., Shamloo, M., Nikolich, K. J. Neurochem. (2006) [Pubmed]
  11. Homer1 proteins and AMPA receptors modulate cocaine-induced behavioural plasticity. Ghasemzadeh, M.B., Permenter, L.K., Lake, R., Worley, P.F., Kalivas, P.W. Eur. J. Neurosci. (2003) [Pubmed]
  12. Glutamate transmission and addiction to cocaine. Kalivas, P.W., McFarland, K., Bowers, S., Szumlinski, K., Xi, Z.X., Baker, D. Ann. N. Y. Acad. Sci. (2003) [Pubmed]
  13. Involvement of unique leucine-zipper motif of PSD-Zip45 (Homer 1c/vesl-1L) in group 1 metabotropic glutamate receptor clustering. Tadokoro, S., Tachibana, T., Imanaka, T., Nishida, W., Sobue, K. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  14. Subfield-specific immediate early gene expression associated with hippocampal long-term potentiation in vivo. French, P.J., O'Connor, V., Jones, M.W., Davis, S., Errington, M.L., Voss, K., Truchet, B., Wotjak, C., Stean, T., Doyère, V., Maroun, M., Laroche, S., Bliss, T.V. Eur. J. Neurosci. (2001) [Pubmed]
  15. Isolation of PSD-Zip45, a novel Homer/vesl family protein containing leucine zipper motifs, from rat brain. Sun, J., Tadokoro, S., Imanaka, T., Murakami, S.D., Nakamura, M., Kashiwada, K., Ko, J., Nishida, W., Sobue, K. FEBS Lett. (1998) [Pubmed]
  16. The postsynaptic scaffold proteins ProSAP1/Shank2 and Homer1 are associated with glutamate receptor complexes at rat retinal synapses. Brandstätter, J.H., Dick, O., Boeckers, T.M. J. Comp. Neurol. (2004) [Pubmed]
  17. Synaptic targeting of PSD-Zip45 (Homer 1c) and its involvement in the synaptic accumulation of F-actin. Usui, S., Konno, D., Hori, K., Maruoka, H., Okabe, S., Fujikado, T., Tano, Y., Sobue, K. J. Biol. Chem. (2003) [Pubmed]
  18. Structure of the Homer EVH1 domain-peptide complex reveals a new twist in polyproline recognition. Beneken, J., Tu, J.C., Xiao, B., Nuriya, M., Yuan, J.P., Worley, P.F., Leahy, D.J. Neuron (2000) [Pubmed]
  19. Homer binds a novel proline-rich motif and links group 1 metabotropic glutamate receptors with IP3 receptors. Tu, J.C., Xiao, B., Yuan, J.P., Lanahan, A.A., Leoffert, K., Li, M., Linden, D.J., Worley, P.F. Neuron (1998) [Pubmed]
  20. Homer proteins regulate coupling of group I metabotropic glutamate receptors to N-type calcium and M-type potassium channels. Kammermeier, P.J., Xiao, B., Tu, J.C., Worley, P.F., Ikeda, S.R. J. Neurosci. (2000) [Pubmed]
  21. Regulation of dendritic spine morphology and synaptic function by Shank and Homer. Sala, C., Piëch, V., Wilson, N.R., Passafaro, M., Liu, G., Sheng, M. Neuron (2001) [Pubmed]
  22. Amygdalar and prefrontal pathways to the lateral hypothalamus are activated by a learned cue that stimulates eating. Petrovich, G.D., Holland, P.C., Gallagher, M. J. Neurosci. (2005) [Pubmed]
  23. Homer-1 mRNA in the rat suprachiasmatic nucleus is regulated differentially by the retinohypothalamic tract transmitters pituitary adenylate cyclase activating polypeptide and glutamate at time points where light phase-shifts the endogenous rhythm. Nielsen, H.S., Georg, B., Hannibal, J., Fahrenkrug, J. Brain Res. Mol. Brain Res. (2002) [Pubmed]
  24. Endothelin-1 activates Homer 1alpha expression via mitogen-activated protein kinase in cardiac myocytes. Kawamoto, T., Togi, K., Yamauchi, R., Yoshida, Y., Nakashima, Y., Kita, T., Tanaka, M. Int. J. Mol. Med. (2006) [Pubmed]
  25. Novel members of the Vesl/Homer family of PDZ proteins that bind metabotropic glutamate receptors. Kato, A., Ozawa, F., Saitoh, Y., Fukazawa, Y., Sugiyama, H., Inokuchi, K. J. Biol. Chem. (1998) [Pubmed]
  26. Increased levels of Homer1b/c and Shank1a in the post-synaptic density of spinal dorsal horn neurons are associated with neuropathic pain in rats. Miletic, G., Miyabe, T., Gebhardt, K.J., Miletic, V. Neurosci. Lett. (2005) [Pubmed]
  27. Deep brain stimulation in a rat model modulates TH, CaMKIIa and Homer1 gene expression. Henning, J., Koczan, D., Glass, A., Karopka, T., Pahnke, J., Rolfs, A., Benecke, R., Gimsa, U. Eur. J. Neurosci. (2007) [Pubmed]
  28. Topology of Homer 1c and Homer 1a in C2C12 myotubes and transgenic skeletal muscle fibers. Volpe, P., Sandri, C., Bortoloso, E., Valle, G., Nori, A. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  29. Evidence for the presence of two homer 1 transcripts in skeletal and cardiac muscles. Sandonà, D., Tibaldo, E., Volpe, P. Biochem. Biophys. Res. Commun. (2000) [Pubmed]
  30. Co-expression of metabotropic glutamate receptor type 1alpha with homer-1a/Vesl-1S increases the cell surface expression of the receptor. Ciruela, F., Soloviev, M.M., McIlhinney, R.A. Biochem. J. (1999) [Pubmed]
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