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Gene Review

Homer2  -  homer homolog 2 (Drosophila)

Mus musculus

Synonyms: 9330120H11Rik, AW539445, CPD, Cupidin, Homer protein homolog 2, ...
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Disease relevance of Homer2

  • Swelling during early stages of ethanol dehydration can be prevented by using 70% or 100% ethanol as the first step, with marginal reduction in the post CPD volume and no apparent differences in the SEM [1].

High impact information on Homer2

  • Here, we report that deletion of Homer1 or Homer2 in mice caused the same increase in sensitivity to cocaine-induced locomotion, conditioned reward, and augmented extracellular glutamate in nucleus accumbens as that elicited by withdrawal from repeated cocaine administration [2].
  • Moreover, adeno-associated virus-mediated restoration of Homer2 in the accumbens of Homer2 KO mice reversed the cocaine-sensitized phenotype [2].
  • Further analysis of Homer2 KO mice revealed extensive additional behavioral and neurochemical similarities to cocaine-sensitized animals, including accelerated acquisition of cocaine self-administration and altered regulation of glutamate by metabotropic glutamate receptors and cystine/glutamate exchange [2].
  • Characterization of Ca2+ signaling in pancreatic acinar cells from Homer2-/- and Homer3-/- mice showed that Homer 3 has no discernible role in Ca2+ signaling in these cells [3].
  • Homer 2 tunes G protein-coupled receptors stimulus intensity by regulating RGS proteins and PLCbeta GAP activities [3].

Biological context of Homer2

  • Homer2 is necessary for EtOH-induced neuroplasticity [4].
  • In this report we summarize the behavioral and neurochemical effects of Homer2 gene deletion in mice and compare this with the effects of chronic cocaine treatment in rats [5].
  • Constitutive Homer2 gene deletion [knock-out (KO)] and rescue with adeno-associated viral (AAV) transfection of Homer2b was used to demonstrate the importance of Homer proteins in neuroplasticity produced by repeated ethanol (EtOH) administration [4].
  • Moreover, Homer 2 preferentially bound to PLCbeta in pancreatic acini and brain extracts and stimulated GAP activity of RGS4 and of PLCbeta in an in vitro reconstitution system, with minimal effect on PLCbeta-mediated PIP2 hydrolysis [3].
  • The current studies examined whether hematopoiesis in the bone marrow and T-cell development in the thymus were attenuated in young adult A/J mice fed a moderately low protein diet (MPD, 50 g protein/kg) for 15 wk compared with mice fed a control protein diet (CPD, 180 g protein/kg) [6].

Anatomical context of Homer2

  • Cupidin (Homer 2/vesl-2) is a post-synaptic adaptor protein that associates with glutamate receptor complexes and the actin cytoskeleton [7].
  • Homer 1b/c and Cupidin/Homer 2a/b are widespread throughout the developing brain and are down-regulated in hindbrain-origin regions, such as the cerebellum, pons, and medulla oblongata [8].
  • Moving (and overall) least-squares spectra before trauma detected in EPD (versus CPD) pronounced 3.5-day (circasemiseptan) and 8-h oscillations corresponding to components of the endothelin-1 chronome in human blood plasma reported earlier [9].

Associations of Homer2 with chemical compounds

  • Evidence for a relationship between Group 1 mGluR hypofunction and increased cocaine and ethanol sensitivity in Homer2 null mutant mice [10].
  • In contrast to glutamate, Homer2 KO mice showed a normal increase in extracellular dopamine following a cocaine challenge injection [5].
  • Using peptide library screenings, we present data that demonstrate the high affinity of the Vesl 2 EVH1 domain towards peptide sequences containing a proline-rich core sequence (PPSPF) that requires additional charged amino acid residues on either side for specific binding [11].
  • Several active site-directed inhibitors also show generally similar potency toward the two enzymes, although guanidinoethylmercaptosuccinic acid is approximately 10-fold more potent, and hippuryl-Arg is approximately 100-fold more potent as an inhibitor of CPD than of CPE [12].
  • DPP was formed by the reaction of reduced DDAVP with Pal-CPD [13].
  • NAC Homer2 overexpression facilitated NAC glutamate and dopamine release following an acute alcohol injection and augmented alcohol-induced dopamine and glutamate sensitization, but did not affect NAC gamma-aminobutyric acid levels [14].

Physical interactions of Homer2

  • Hippi interacted specifically with Homer1c but not with its homologue Homer2 [15].
  • In cultured granule cells 7 days in vitro, Cupidin was present as synaptic and extra-synaptic punctate clusters that largely co-localized with the actin-cytoskeletal binding partners F-actin and drebrin, as well as a post-synaptic scaffold protein PSD-95 [7].

Other interactions of Homer2

  • Together, our findings indicate that Cupidin may serve as a postsynaptic scaffold protein that links mGluR signaling with actin cytoskeleton and Rho family proteins, perhaps during the dynamic phase of morphological changes that occur during synapse formation in cerebellar granule cells [16].

Analytical, diagnostic and therapeutic context of Homer2

  • Subsequently, a new set of mice were provided with CPD and a low protein diet (LPD, 25 g protein/kg) [6].


  1. Morphological correlations with dimensional change during SEM specimen preparation. Boyde, A., Maconnachie, E. Scanning electron microscopy. (1981) [Pubmed]
  2. 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]
  3. Homer 2 tunes G protein-coupled receptors stimulus intensity by regulating RGS proteins and PLCbeta GAP activities. Shin, D.M., Dehoff, M., Luo, X., Kang, S.H., Tu, J., Nayak, S.K., Ross, E.M., Worley, P.F., Muallem, S. J. Cell Biol. (2003) [Pubmed]
  4. 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]
  5. Homer2 gene deletion in mice produces a phenotype similar to chronic cocaine treated rats. Kalivas, P.W., Szumlinski, K.K., Worley, P. Neurotoxicity research. (2004) [Pubmed]
  6. Chronic consumption of a moderately low protein diet does not alter hematopoietic processes in young adult mice. Huang, Z.L., Fraker, P.J. J. Nutr. (2003) [Pubmed]
  7. Glutamate-induced declustering of post-synaptic adaptor protein Cupidin (Homer 2/vesl-2) in cultured cerebellar granule cells. Shiraishi, Y., Mizutani, A., Yuasa, S., Mikoshiba, K., Furuichi, T. J. Neurochem. (2003) [Pubmed]
  8. 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]
  9. About 8- and approximately 84-h rhythms in endotheliocytes as in endothelin-1 and effect of trauma. Katinas, G.S., Halberg, F., Cornélissen, G., Hawkins, D., Bueva, M.V., Korzhevsky, D.E., Sapozhnikova, L.R., Rhodus, N., Schaffer, E. Peptides (2001) [Pubmed]
  10. Evidence for a relationship between Group 1 mGluR hypofunction and increased cocaine and ethanol sensitivity in Homer2 null mutant mice. Szumlinski, K.K., Toda, S., Middaugh, L.D., Worley, P.F., Kalivas, P.W. Ann. N. Y. Acad. Sci. (2003) [Pubmed]
  11. The N-terminal domain of Homer/Vesl is a new class II EVH1 domain. Barzik, M., Carl, U.D., Schubert, W.D., Frank, R., Wehland, J., Heinz, D.W. J. Mol. Biol. (2001) [Pubmed]
  12. Purification and characterization of carboxypeptidase D, a novel carboxypeptidase E-like enzyme, from bovine pituitary. Song, L., Fricker, L.D. J. Biol. Chem. (1995) [Pubmed]
  13. Preparation, purification, and characterization of a reversibly lipidized desmopressin with potentiated anti-diuretic activity. Wang, J., Shen, D., Shen, W.C. Pharm. Res. (1999) [Pubmed]
  14. Accumbens Homer2 overexpression facilitates alcohol-induced neuroplasticity in C57BL/6J mice. Szumlinski, K.K., Ary, A.W., Lominac, K.D., Klugmann, M., Kippin, T.E. Neuropsychopharmacology (2008) [Pubmed]
  15. Homer1c interacts with Hippi and protects striatal neurons from apoptosis. Sakamoto, K., Yoshida, S., Ikegami, K., Minakami, R., Kato, A., Udo, H., Sugiyama, H. Biochem. Biophys. Res. Commun. (2007) [Pubmed]
  16. 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]
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