Journal: Journal of Molecular Medicine (Berlin, Germany)

Article Title: Impact of HOMER2 frameshift extension variant on auditory function and development

doi: 10.1007/s00109-025-02556-7

Figure Lengend Snippet: Pedigree, audiometric profile, genetic analysis, and post-cochlear implantation speech outcomes from SB1190-1923 (F/61). a Pedigree of SB1190: the proband (F/61) carries the previously unreported, novel HOMER2 variant (c.1033 del (p.Arg345Glu fs *64)) which is associated with DFNA68. Low pLI score (0.01) of HOMER2 suggests that alteration of HOMER2 exerts a pathogenic effect via a mechanism other than loss-of-function. Both parents of SB1190-1923 passed away in their early 70 s without showing any signs of significant hearing loss, and none of the SB1190-1923’s children exhibited any symptoms of hearing loss. b Preoperative pure tone audiograms show profound down-sloping sensorineural hearing loss with 8% speech discrimination score bilaterally. c Post-Cochlear Implantation speech outcome speech recognition improves significantly at 3- and 6-months post-implantation across various syllable and sentence conditions. F , female; pLI , intolerant; CI , cochlear implantation

Article Snippet: The HOMER2 tagged ORF clone ( NM_199330 ) was obtained from OriGene (RC223154).

Techniques: Variant Assay

Journal: Journal of Molecular Medicine (Berlin, Germany)

Article Title: Impact of HOMER2 frameshift extension variant on auditory function and development

doi: 10.1007/s00109-025-02556-7

Figure Lengend Snippet: Predicted 3D structures of HOMER2 WT and HOMER2 p.R345E fs *64 using AlphaFold2. a Structural alignment of HOMER2 WT and HOMER2 p.R345E fs *64. The EVH1 domain is highlighted in the yellow area, and the coiled-coil (CC) domain is marked by the blue dashed line. a1 The hydrogen bond between N43 and A113 is disrupted in HOMER2 p.R345E fs *64 compared to HOMER2 WT. a2 The β-sheet structure in HOMER2 p.R345E fs *64 extends to F90, and a hydrogen bond forms between F74 and S71, which is absent in HOMER2 WT. b The structure of the HOMER1 [ NP_004263.1 ] and HOMER2 dimer is shown. HOMER1 is depicted in gray, while HOMER2 WT, HOMER2 p.R345E fs *64, and HOMER2 p.R345* are represented in green, brown, and purple, respectively. The coiled-coil region of HOMER2, which can interact with other proteins, is located at amino acids 307–329 in the WT and is shifted to amino acids 275–297 in the HOMER2 variants. c Structural changes in the EVH1 domain were detected in the HOMER1 WT and HOMER2 variants dimer. The distance between each EVH1 domain of HOMER1 and HOMER2 p.R345E fs *64 was reduced ( b ) compared to the WT, which is shifted vertically. In HOMER1 WT and HOMER2 p.R345* dimer, the distance between each EVH1 was increased ( b ) and slightly shifted vertically. d The predicted tetramer structures were obtained using HOMER1 and HOMER2. Two HOMER1 proteins were combined with two HOMER2 WT, two HOMER2 p.R345E fs *64, or two HOMER2 p.R345* molecules. In the HOMER1 and HOMER2 p.R345E fs *64 tetramer, the location of the EVH1 domain of HOMER1 was altered, and the C-terminal of HOMER2 approached the EVH1 domain of HOMER2 (dashed black box). In the HOMER1 and HOMER2 p.R345* tetramer, HOMER1 and HOMER2 formed homodimers, and each homodimer formed a tetramer, unlike the other configurations. WT , wild-type; R , arginine; E , glutamate; fs , frameshift; EVH1 , Ena/Vasp homology domain 1; F , phenylalanine; S , serine; N , asparagine; A , alanine

Article Snippet: The HOMER2 tagged ORF clone ( NM_199330 ) was obtained from OriGene (RC223154).

Techniques:

Journal: Journal of Molecular Medicine (Berlin, Germany)

Article Title: Impact of HOMER2 frameshift extension variant on auditory function and development

doi: 10.1007/s00109-025-02556-7

Figure Lengend Snippet: Cardiac and morphological defects in zebrafish larvae injected with HOMER2 mRNA. a Representative images of zebrafish larvae at 3 dpf displaying varying degrees of heart malformations. The larvae were categorized into four groups: normal, mild, and severe heart defects based on the degree of cardiac enlargement, and an additional group with general abnormal morphology. The categories include normal, mild, and severe heart defects, with red arrowheads marking the regions of cardiac deformity. Additionally, larvae with abnormal overall morphology are shown. b Bar graph illustrating the distribution of larvae with heart and morphological abnormalities in the different experimental groups: uninjected control, RFP control, HOMER2 WT, HOMER2 p.R345*, and HOMER2 p.R345E fs *64. Chi-squared analysis was used to compare the proportions of defects between groups, with significant differences indicated. (**** p < 0.0001, *** p < 0.001, ** p < 0.01, * p < 0.05). n = 100 per group. dpf , days post-fertilization; RFP , red fluorescent protein; WT , wild-type; R , arginine; E , glutamate; fs , frameshift

Article Snippet: The HOMER2 tagged ORF clone ( NM_199330 ) was obtained from OriGene (RC223154).

Techniques: Injection, Control

Journal: Journal of Molecular Medicine (Berlin, Germany)

Article Title: Impact of HOMER2 frameshift extension variant on auditory function and development

doi: 10.1007/s00109-025-02556-7

Figure Lengend Snippet: Otic capsule area in zebrafish larvae at 3 days post-fertilization. a Representative image of 3 dpf zebrafish larvae, with the otic capsule indicated by a red dashed circle. b Bar graph showing the measured otic capsule area in control, RFP control, HOMER2 WT, HOMER2 p.R345*, and HOMER2 p.R345E fs *64 groups. No statistically significant differences were observed between groups ( p > 0.05). n = 15 per group. dpf , days post-fertilization; RFP , red fluorescent protein; WT , wild-type; R , arginine; E , glutamate; fs , frameshift

Article Snippet: The HOMER2 tagged ORF clone ( NM_199330 ) was obtained from OriGene (RC223154).

Techniques: Control

Journal: Journal of Molecular Medicine (Berlin, Germany)

Article Title: Impact of HOMER2 frameshift extension variant on auditory function and development

doi: 10.1007/s00109-025-02556-7

Figure Lengend Snippet: Analysis of hair cell numbers in zebrafish neuromasts. a Representative image of the four neuromasts (SO1, SO2, O1, and OC1) from each group: control, RFP control, HOMER2 WT, HOMER2 p.R345*, and HOMER2 p.R345E fs *64. b Bar graph comparing each group's average number of hair cells across the four neuromasts. No statistically significant differences were observed between the groups ( p > 0.05). n = 10 per group. SO1 , supraorbital1; SO2 , supraorbital2; O1 , otic; OC1 , occipital; RFP , red fluorescent protein; WT , wild-type; R , arginine; E , glutamate; fs , frameshift

Article Snippet: The HOMER2 tagged ORF clone ( NM_199330 ) was obtained from OriGene (RC223154).

Techniques: Control

Journal: Journal of Molecular Medicine (Berlin, Germany)

Article Title: Impact of HOMER2 frameshift extension variant on auditory function and development

doi: 10.1007/s00109-025-02556-7

Figure Lengend Snippet: Comparison of FM1-43 uptake in zebrafish neuromast hair cells. a Representative image of neuromast hair cells in control, RFP control, HOMER2 WT, and HOMER2 variant groups. Hair cells are labeled with GFP, and FM1-43 uptake is indicated by mCherry fluorescence. b Bar graph comparing the fluorescence intensity of FM1-43 uptake across groups. While no significant differences were observed between the control, RFP, and HOMER2 WT groups, the HOMER2 variant groups showed a statistically significant reduction in intensity compared to the RFP group (* p < 0.05, ** p < 0.01). n = 5 per group. RFP , red fluorescent protein; WT , wild-type

Article Snippet: The HOMER2 tagged ORF clone ( NM_199330 ) was obtained from OriGene (RC223154).

Techniques: Comparison, Control, Variant Assay, Labeling, Fluorescence

Journal: Journal of Molecular Medicine (Berlin, Germany)

Article Title: Impact of HOMER2 frameshift extension variant on auditory function and development

doi: 10.1007/s00109-025-02556-7

Figure Lengend Snippet: Comparison of startle reflex in zebrafish larvae at 6 days post-fertilization. a Bar graph depicting the latency (time from stimulus application to the onset of movement) across the control, RFP control, HOMER2 WT, HOMER2 p.R345*, and HOMER2 p.R345E fs *64 groups. The latency was significantly longer in the HOMER2 p.R345E fs *64 group compared to HOMER2 WT ( p < 0.05). b Bar graph showing the distance moved during the startle response. The HOMER2 p.R345E fs *64 groups exhibited a significant reduction in distance moved compared to HOMER2 WT and p.R345*, and showed a further reduction relative to the RFP control group ( p < 0.05). n = 20 per group. RFP , red fluorescent protein; WT , wild-type; R , arginine; E , glutamate; fs , frameshift

Article Snippet: The HOMER2 tagged ORF clone ( NM_199330 ) was obtained from OriGene (RC223154).

Techniques: Comparison, Control

Journal: Pathology

Article Title: Overexpression of HOMER2 predicts better outcome in low-grade endometrioid endometrial adenocarcinoma

doi: 10.1016/j.pathol.2018.03.004

Figure Lengend Snippet: (A) Strong (2–3+) immunohistochemical staining with HOMER2. (B) Negative (0–1+) immunohistochemical staining with HOMER2.

Article Snippet: Antigen retrieval was performed by heating in the microwave for 20 min, before incubating the sections with a polyclonal recombinant protein HOMER2 antibody (1:50, 60 min; Novus Biologicals, USA).

Techniques: Immunohistochemical staining, Staining

Journal: Pathology

Article Title: Overexpression of HOMER2 predicts better outcome in low-grade endometrioid endometrial adenocarcinoma

doi: 10.1016/j.pathol.2018.03.004

Figure Lengend Snippet: Correlation of HOMER2 expression and clinical and pathological data

Article Snippet: Antigen retrieval was performed by heating in the microwave for 20 min, before incubating the sections with a polyclonal recombinant protein HOMER2 antibody (1:50, 60 min; Novus Biologicals, USA).

Techniques: Expressing

Journal: Pathology

Article Title: Overexpression of HOMER2 predicts better outcome in low-grade endometrioid endometrial adenocarcinoma

doi: 10.1016/j.pathol.2018.03.004

Figure Lengend Snippet: Survival curve for group 1 cohort showing better cause-specific survival in patients with a strong HOMER2 expression.

Article Snippet: Antigen retrieval was performed by heating in the microwave for 20 min, before incubating the sections with a polyclonal recombinant protein HOMER2 antibody (1:50, 60 min; Novus Biologicals, USA).

Techniques: Expressing

Journal: Pathology

Article Title: Overexpression of HOMER2 predicts better outcome in low-grade endometrioid endometrial adenocarcinoma

doi: 10.1016/j.pathol.2018.03.004

Figure Lengend Snippet: Multivariate analysis for endometrial cancer-specific survival in endometrioid adenocarcinoma

Article Snippet: Antigen retrieval was performed by heating in the microwave for 20 min, before incubating the sections with a polyclonal recombinant protein HOMER2 antibody (1:50, 60 min; Novus Biologicals, USA).

Techniques:

Journal: Nature neuroscience

Article Title: Synaptic depression via mGluR1 positive allosteric modulation suppresses cue-induced cocaine craving

doi: 10.1038/nn.3590

Figure Lengend Snippet: (a) Co-immunoprecipitation (co-IP) experiments assessing the physical associations between mGluR1 and Homer proteins on withdrawal day (WD) 14, 25 or 48 from extended-access cocaine (coc) or saline (sal) self-administration (see timeline in ). No significant changes in association between mGluR1 and Homer proteins were observed at any of the 3 withdrawal time-points. ( b ) In the case of mGluR5, no change in association with Homer proteins was observed at the two earlier withdrawal time-points (WD14 and WD25). However, a significant decrease in association between mGluR5 and both Homer isoforms was found on WD48 in animals that previously self-administered cocaine. Data are expressed as percent of Saline group (± s.e.m.) at each time-point (n values are provided within each bar). **p=0.01 (Homer1bc) and *p=0.04 (Homer2) versus respective Saline groups. Full-length blots are presented in .

Article Snippet: Validation is provided on the supplier’s website for all antibodies utilized, as well as on Antibodypedia for Homer1bc (Santa Cruz) and Homer2 (Abnova).

Techniques: Immunoprecipitation, Co-Immunoprecipitation Assay, Saline

Journal: Nature neuroscience

Article Title: Synaptic depression via mGluR1 positive allosteric modulation suppresses cue-induced cocaine craving

doi: 10.1038/nn.3590

Figure Lengend Snippet: ( a ) Timeline (SA, self-administration). To assess the effects of Homer overexpression on incubation of cocaine craving, viruses (AAV-GFP, Homer1c or Homer2) were injected into the NAc core at the same time that animals underwent jugular catheterization surgery, allowing Homer expression to peak during early withdrawal. ( b ) Staining for the HA tag on cDNA-Homer1c verified localized overexpression in the NAc core (20X magnification; image taken ~3 months after virus injection; scale bar, 100μm; ac, anterior commissure). ( c ) Following ~1 week of recovery from surgeries, animals self-administered cocaine (0.5 mg/kg) for 6 h/day for 10 days. No difference in cocaine intake (average infusions obtained each day ± s.e.m.) was observed between the 3 groups. ( d ) All animals showed an increase in cue-induced cocaine-seeking on WD48 compared to WD1 (i.e., incubation), regardless of which virus infusion they received. ***p<0.001, **p=0.01, WD1 versus WD48 (ANOVA followed by least significant difference post-hoc comparisons); GFP, n=10 rats; Homer1c, n=8 rats; Homer2, n=10 rats.

Article Snippet: Validation is provided on the supplier’s website for all antibodies utilized, as well as on Antibodypedia for Homer1bc (Santa Cruz) and Homer2 (Abnova).

Techniques: Over Expression, Incubation, Injection, Expressing, Staining, Virus