HOMER1

Homer homolog 1 (Drosophila)

PDB rendering based on 1ddv.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
SymbolsHOMER1 ; HOMER; HOMER1A; HOMER1B; HOMER1C; SYN47; Ves-1
External IDsOMIM: 604798 MGI: 1347345 HomoloGene: 3155 GeneCards: HOMER1 Gene
RNA expression pattern
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez945626556
EnsemblENSG00000152413ENSMUSG00000007617
UniProtQ86YM7Q9Z2Y3
RefSeq (mRNA)NM_001277077NM_001284189
RefSeq (protein)NP_001264006NP_001271118
Location (UCSC)Chr 5:
78.67 – 78.81 Mb		Chr 13:
93.3 – 93.4 Mb
PubMed search

Homer protein homolog 1 or Homer1 is a neuronal protein that in humans is encoded by the HOMER1 gene.[1][2][3] Other names are Vesl and PSD-Zip45.

Structure

Homer1 protein has an N-terminal EVH1 domain, involved in protein interaction, and a C-terminal coiled-coil domain involved in self association. It consists of two major splice variants, short-form (Homer1a) and long-form (Homer1b and c). Homer1a has only EVH1 domain and is monomeric while Homer1b and 1c have both EVH1 and coiled-coil domains and are tetrameric.[4][5] The coiled-coil can be further separated into N-terminal half and C-terminal half. The N-terminal half of the coiled-coil domain is predicted to be a parallel dimer while the C-terminus half is a hybrid of dimeric and anti-parallel tetrameric coiled-coil. As a whole, long Homer is predicted to have a dumbbell-like structure where two pairs of EVH1 domains are located on two sides of long (~50 nm) coiled-coil domain.[5] Mammals have Homer2 and Homer3, in addition to Homer1, which have similar domain structure. They also have similar alternatively spliced forms.

Dimeric-tetrameric coiled-coil domain of Homer1b. PDB rendering based on 3CVE.

Tissue distribution

Homer1 is expressed widely in the central nervous system as well as peripheral tissue including heart, kidney, ovary, testis, and skeletal muscle. Subcellularly in neurons, Homer1 is concentrated in postsynaptic structures and constitutes a major part of the postsynaptic density.

Function

EVH1 domain interacts with PPXXF motif. This sequence motif exists in group 1 metabotrophic glutamate receptor (mGluR1 and mGluR5), IP3 receptors (IP3R), Shank, transient receptor potential canonical (TRPC) family channels, drebrin, oligophrenin, dynamin3, CENTG1, and ryanodin receptor.[1][3][6][7][8][9] Through its tetrameric structure, long forms of Homer (such as Homer1b and Homer1c) are proposed to cross link different proteins. For example, group 1 mGluR is crossed linked with its signaling downstream, IP3 receptor.[6] Also, through crosslinking another multimeric protein Shank, it is proposed to comprise a core of the postsynaptic density.[5]

Notably, the expression of Homer1a is induced by neuronal activity while that of Homer1b and 1c are constitutive. Thus Homer1a is classified as an immediate early gene. Homer1a, acts as a natural dominant negative form that blocks interaction between long-forms and their ligand proteins by competing with the EVH1 binding site on the ligand proteins. In this way, the short form of Homer uncouples mGluR signaling and also shrinks dendritic spine structure.[2][10] Therefore, the short form of Homer is considered to be a part of a mechanism of homeostatic plasticity that dampens the neuronal responsiveness when input activity is too high. The long form Homer1c plays a role in synaptic plasticity and the stabilization of synaptic changes during long-term potentiation.[11]

The coiled-coil domain is reported to interact with syntaxin13 and activated Cdc42. The interaction with Cdc42 inhibit the activity of Cdc42 to remodel dendritic spine structure.

See also


References

  1. ↑ 1.0 1.1 Shiraishi-Yamaguchi Y, Furuichi T (2007). "The Homer family proteins". Genome Biol. 8 (2): 206. doi:10.1186/gb-2007-8-2-206. PMC 1852408. PMID 17316461.
  2. ↑ 2.0 2.1 Tu JC, Xiao B, Yuan JP, Lanahan AA, Leoffert K, Li M et al. (Dec 1998). "Homer binds a novel proline-rich motif and links group 1 metabotropic glutamate receptors with IP3 receptors". Neuron 21 (4): 717–26. doi:10.1016/S0896-6273(00)80589-9. PMID 9808459.
  3. ↑ 3.0 3.1 "Entrez Gene: HOMER1 homer homolog 1 (Drosophila)".
  4. ↑ Hayashi MK, Ames HM, Hayashi Y (Aug 2006). "Tetrameric hub structure of postsynaptic scaffolding protein homer". J Neurosci. 26 (33): 8492–501. doi:10.1523/JNEUROSCI.2731-06.2006. PMID 16914674.
  5. ↑ 5.0 5.1 5.2 Hayashi MK, Tang C, Verpelli C, Narayanan R, Stearns MH, Xu RM et al. (Apr 2009). "The postsynaptic density proteins Homer and Shank form a polymeric network structure". Cell 137 (1): 159–71. doi:10.1016/j.cell.2009.01.050. PMC 2680917. PMID 19345194.
  6. ↑ 6.0 6.1 Xiao B, Tu JC, Petralia RS, Yuan JP, Doan A, Breder CD et al. (Dec 1998). "Homer regulates the association of group 1 metabotropic glutamate receptors with multivalent complexes of homer-related, synaptic proteins". Neuron 21 (4): 707–16. doi:10.1016/S0896-6273(00)80588-7. PMID 9808458.
  7. ↑ Rong R, Ahn JY, Huang H, Nagata E, Kalman D, Kapp JA et al. (Nov 2003). "PI3 kinase enhancer-Homer complex couples mGluRI to PI3 kinase, preventing neuronal apoptosis". Nat. Neurosci. 6 (11): 1153–61. doi:10.1038/nn1134. PMID 14528310.
  8. ↑ Hwang SY, Wei J, Westhoff JH, Duncan RS, Ozawa F, Volpe P et al. (Aug 2003). "Differential functional interaction of two Vesl/Homer protein isoforms with ryanodine receptor type 1: a novel mechanism for control of intracellular calcium signaling". Cell Calcium 34 (2): 177–84. doi:10.1016/S0143-4160(03)00082-4. PMID 12810060.
  9. ↑ Feng W, Tu J, Yang T, Vernon PS, Allen PD, Worley PF et al. (Nov 2002). "Homer regulates gain of ryanodine receptor type 1 channel complex". J. Biol. Chem. 277 (47): 44722–30. doi:10.1074/jbc.M207675200. PMID 12223488.
  10. ↑ Sala C, Futai K, Yamamoto K, Worley PF, Hayashi Y, Sheng M (Jul 2003). "Inhibition of dendritic spine morphogenesis and synaptic transmission by activity-inducible protein Homer1a". J Neurosci 23 (15): 6327–37. PMID 12867517.
  11. ↑ Meyer D, Bonhoeffer T, Scheuss V (2014). "Balance and stability of synaptic structures during synaptic plasticity". Neuron 82 (2): 430–43. doi:10.1016/j.neuron.2014.02.031. PMID 24742464.

Further reading

  • Xiao B, Tu JC, Worley PF (2000). "Homer: a link between neural activity and glutamate receptor function". Curr. Opin. Neurobiol. 10 (3): 370–4. doi:10.1016/S0959-4388(00)00087-8. PMID 10851183.
  • Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
  • Hillier LD, Lennon G, Becker M, Bonaldo MF, Chiapelli B, Chissoe S et al. (1997). "Generation and analysis of 280,000 human expressed sequence tags". Genome Res. 6 (9): 807–28. doi:10.1101/gr.6.9.807. PMID 8889549.
  • Brakeman PR, Lanahan AA, O'Brien R, Roche K, Barnes CA, Huganir RL et al. (1997). "Homer: a protein that selectively binds metabotropic glutamate receptors". Nature 386 (6622): 284–8. doi:10.1038/386284a0. PMID 9069287.
  • Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
  • Tu JC, Xiao B, Naisbitt S, Yuan JP, Petralia RS, Brakeman P et al. (1999). "Coupling of mGluR/Homer and PSD-95 complexes by the Shank family of postsynaptic density proteins". Neuron 23 (3): 583–92. doi:10.1016/S0896-6273(00)80810-7. PMID 10433269.
  • Roche KW, Tu JC, Petralia RS, Xiao B, Wenthold RJ, Worley PF (1999). "Homer 1b regulates the trafficking of group I metabotropic glutamate receptors". J. Biol. Chem. 274 (36): 25953–7. doi:10.1074/jbc.274.36.25953. PMID 10464340.
  • Minakami R, Kato A, Sugiyama H (2000). "Interaction of Vesl-1L/Homer 1c with syntaxin 13". Biochem. Biophys. Res. Commun. 272 (2): 466–71. doi:10.1006/bbrc.2000.2777. PMID 10833436.
  • Ango F, Prézeau L, Muller T, Tu JC, Xiao B, Worley PF et al. (2001). "Agonist-independent activation of metabotropic glutamate receptors by the intracellular protein Homer". Nature 411 (6840): 962–5. doi:10.1038/35082096. PMID 11418862. Vancouver style error (help)
  • Wistow G, Bernstein SL, Wyatt MK, Fariss RN, Behal A, Touchman JW et al. (2002). "Expressed sequence tag analysis of human RPE/choroid for the NEIBank Project: over 6000 non-redundant transcripts, novel genes and splice variants". Mol. Vis. 8: 205–20. PMID 12107410.
  • Feng W, Tu J, Yang T, Vernon PS, Allen PD, Worley PF et al. (2003). "Homer regulates gain of ryanodine receptor type 1 channel complex". J. Biol. Chem. 277 (47): 44722–30. doi:10.1074/jbc.M207675200. PMID 12223488.
  • Hwang SY, Wei J, Westhoff JH, Duncan RS, Ozawa F, Volpe P et al. (2004). "Differential functional interaction of two Vesl/Homer protein isoforms with ryanodine receptor type 1: a novel mechanism for control of intracellular calcium signaling". Cell Calcium 34 (2): 177–84. doi:10.1016/S0143-4160(03)00082-4. PMID 12810060.
  • Norton N, Williams HJ, Williams NM, Spurlock G, Zammit S, Jones G et al. (2004). "Mutation screening of the Homer gene family and association analysis in schizophrenia". Am. J. Med. Genet. B Neuropsychiatr. Genet. 120 (1): 18–21. doi:10.1002/ajmg.b.20032. PMID 12815733.
  • Westhoff JH, Hwang SY, Duncan RS, Ozawa F, Volpe P, Inokuchi K et al. (2004). "Vesl/Homer proteins regulate ryanodine receptor type 2 function and intracellular calcium signaling". Cell Calcium 34 (3): 261–9. doi:10.1016/S0143-4160(03)00112-X. PMID 12887973.
  • Yuan JP, Kiselyov K, Shin DM, Chen J, Shcheynikov N, Kang SH et al. (2003). "Homer binds TRPC family channels and is required for gating of TRPC1 by IP3 receptors". Cell 114 (6): 777–89. doi:10.1016/S0092-8674(03)00716-5. PMID 14505576.
  • Rong R, Ahn JY, Huang H, Nagata E, Kalman D, Kapp JA et al. (2003). "PI3 kinase enhancer-Homer complex couples mGluRI to PI3 kinase, preventing neuronal apoptosis". Nat. Neurosci. 6 (11): 1153–61. doi:10.1038/nn1134. PMID 14528310.