| 1999 |
Cupidin/Homer2a N-terminal domain (highly conserved EVH1 domain) binds F-actin in vitro and associates with mGluR1; a Cupidin-mGluR1-actin complex was immunoprecipitated from cerebellar lysates. The C-terminal coiled-coil domain binds activated Cdc42 (GTP-dependent) in vitro and functionally interacts with activated Cdc42 in a heterologous expression system. |
In vitro F-actin binding assay, co-immunoprecipitation from cerebellar lysates, yeast two-hybrid and heterologous overexpression with activated Cdc42 |
The Journal of neuroscience |
High |
10493740
|
| 2003 |
Homer2 tunes GPCR signal intensity by: (1) preferentially binding PLCβ in pancreatic acini and brain extracts; (2) stimulating GAP activity of RGS4 and PLCβ in an in vitro reconstitution system (with minimal effect on PLCβ-mediated PIP2 hydrolysis); (3) deletion of Homer2 (but not Homer3) increased agonist potency for PLCβ activation and Ca²⁺ oscillation frequency without altering IP3R localization or channel activity. |
Homer2−/− mouse acinar cells, in vitro reconstitution of RGS/PLCβ GAP activity, co-immunoprecipitation (Homer2–PLCβ), Ca²⁺ imaging |
The Journal of cell biology |
High |
12860966
|
| 2003 |
Cupidin/Homer2 clusters dissociate rapidly upon glutamate stimulation in cerebellar and hippocampal neurons via NMDA receptor-mediated Ca²⁺ influx, followed by MAPK/ERK and protein tyrosine kinase signaling; Ca²⁺-dependent protein phosphatase activity reduces specific Homer2 isoforms post-translationally. Declustering precedes that of F-actin and Drebrin. |
Live-cell immunofluorescence in cultured cerebellar and hippocampal neurons, pharmacological dissection (NMDA antagonists, MAPK/ERK inhibitors, phosphatase inhibitors) |
Journal of neurochemistry |
Medium |
14511114
|
| 2005 |
Homer2 knock-out mice fail to develop ethanol-induced locomotor sensitization, place preference, or augmented extracellular dopamine/glutamate in nucleus accumbens after repeated EtOH; AAV-mediated re-expression of Homer2b in accumbens fully rescues these phenotypes, demonstrating a necessary and active role for accumbens Homer2 in EtOH-induced neuroplasticity. |
Constitutive Homer2 knockout mouse, AAV-mediated Homer2b rescue in nucleus accumbens, in vivo microdialysis, behavioral tests |
The Journal of neuroscience |
High |
16049182
|
| 2005 |
A novel Homer2-specific binding partner, 2B28 (containing UBA, coiled-coil, and UBX domains), was identified by yeast two-hybrid using Homer2b C-terminal half as bait. 2B28 co-localizes with ubiquitin and enhances proteasomal degradation of IκB and Homer1a when expressed in HEK293T cells; 2B28 specifically binds Homer2 but not Homer1. |
Yeast two-hybrid, co-localization in HEK293T cells, western blot for ubiquitin-pathway substrates |
Journal of biochemistry |
Medium |
15944415
|
| 2007 |
HOMER2 was identified as a direct binding partner of MYO18B (class XVIII myosin/tumor suppressor) by yeast two-hybrid; the two proteins co-localize at membrane protrusions and stress fibers (F-actin-rich regions), and HOMER2 expression enhances MYO18B's ability to suppress anchorage-independent growth. |
Yeast two-hybrid, co-localization by immunofluorescence, anchorage-independent growth assay |
Biochemical and biophysical research communications |
Medium |
17386922
|
| 2007 |
Chronic alcohol consumption increases Homer2 protein levels in nucleus accumbens; AAV-mediated overexpression of Homer2b in NAC of C57BL/6J mice augments alcohol reinforcement, preference, conditioned place preference, motor tolerance, and NAC glutamate/dopamine sensitization without affecting GABA levels, indicating Homer2 upregulation is sufficient to promote alcohol neuroplasticity. |
AAV-mediated overexpression in vivo, in vivo microdialysis, behavioral tests (CPP, operant self-administration, tolerance) |
Neuropsychopharmacology |
High |
17568396
|
| 2008 |
Homer2 (and Homer3, but not Homer1) specifically interacts with Amyloid Precursor Protein (APP); their expression inhibits APP processing, reduces Aβ secretion, decreases cell-surface APP, and inhibits maturation of APP and BACE1. |
Co-immunoprecipitation, western blot for APP processing products, Aβ ELISA, cell-surface biotinylation |
Neurobiology of disease |
Medium |
18387811
|
| 2009 |
Cupidin/Homer2 interacts with activated Cdc42 via its C-terminal coiled-coil domain (residues ~191–283). A deletion mutant (Δ191–230) with reduced Cdc42 binding fails to suppress Cdc42-induced filopodia in HeLa cells, is mislocalized to dendritic shafts (not spines), reduces synapse number, decreases mEPSC amplitudes, and decreases Drebrin clustering. The N-terminal EVH1 domain mediates interaction with Drebrin (via Drebrin's Homer ligand motifs). |
Domain deletion mutagenesis, co-immunoprecipitation, HeLa filopodia assay, immunofluorescence in hippocampal neurons, whole-cell electrophysiology (mEPSCs) |
BMC neuroscience |
High |
19309525
|
| 2009 |
Binge alcohol drinking upregulates NAC mGluR5-Homer2-PI3K signaling; mGluR5 with F1128R point mutation (markedly reduced Homer binding) reduces basal NAC PI3K activity and decreases binge drinking by 50%; virus-mediated Homer2b knockdown in NAC attenuates binge alcohol intake. |
Transgenic mGluR5-F1128R knock-in mice, AAV Homer2b knockdown, intra-NAC pharmacology, PI3K activity assay |
The Journal of neuroscience |
High |
19587272
|
| 2012 |
Homer2a/b is characteristic of slow-twitch skeletal muscle and is downregulated early during denervation atrophy. In vivo reconstitution of Homer2 in denervated soleus partially rescues muscle mass, fiber size, and ubiquitination by transcriptionally downregulating MuRF1, Atrogin, and Myogenin. |
In vivo electroporation/transfection of denervated soleus, muscle mass and fiber morphometry, western blot, RT-PCR for atrophy markers |
American journal of physiology. Cell physiology |
Medium |
23076792
|
| 2014 |
Homer2 co-immunoprecipitates with plasma membrane Ca²⁺-ATPase (PMCA) in parotid acinar cells and transfected HEK293 cells via a PPXXF-like motif in PMCA's N-terminus; mutation of this motif specifically abolishes PMCA-Homer2 interaction (but not PMCA-Homer1 interaction) and increases Ca²⁺ clearance. Homer2 deletion markedly increases PMCA4 expression at the apical pole and increases Ca²⁺ extrusion. |
Homer2−/− mouse parotid acinar cells, co-immunoprecipitation, site-directed mutagenesis of PMCA PPXXF motif, Ca²⁺ imaging, western blot/localization |
The Journal of biological chemistry |
High |
25049230
|
| 2015 |
Homer2 deletion reduces NMDA receptor current density in cultured hippocampal neurons at 14 DIV (but not 7 DIV) without affecting kainate receptor currents or GluN2B subunit sensitivity to ifenprodil, and does not alter acute ethanol inhibition of NMDA receptors. |
Whole-cell voltage-clamp electrophysiology in primary hippocampal neurons from Homer2 KO mice |
Synapse |
Medium |
26426435
|
| 2015 |
Homer2 is expressed in stereocilia of hair cells in the murine inner ear; Homer2 knockout mice develop early-onset rapidly progressive hearing loss. A dominant-negative p.Arg185Pro mutation (in the coiled-coil domain essential for multimerization and HOMER2-CDC42 interaction) causes autosomal dominant non-syndromic hearing loss (DFNA68) in humans. |
Homer2 KO mouse auditory phenotyping (ABR), immunofluorescence in inner ear, human genetics (whole exome sequencing + segregation), zebrafish mRNA overexpression of mutant |
PLoS genetics |
High |
25816005
|
| 2019 |
Homer2 and Homer3 interact with NFATc1 and calcineurin; RANKL treatment disrupts Homer-NFATc1 interaction (restored by calcineurin inhibitor cyclosporine A). Deletion of Homer2/Homer3 markedly decreases bone density and facilitates RANKL-induced osteoclast differentiation through increased NFATc1 nuclear translocation, without altering RANKL-induced Ca²⁺ oscillations. |
Homer2/3 double knockout mice, RANKL-treated bone marrow-derived monocytes, co-immunoprecipitation, NFATc1 nuclear translocation assay, bone density measurement (micro-CT), osteoclast differentiation assay |
The Journal of endocrinology |
High |
31319381
|
| 2023 |
CaMKIIα phosphorylates Homer2 at S117/S216; alanine substitution at these sites (Homer2-AA knock-in) prevents activity-dependent phosphorylation of S216 in cortical neurons. Acute cocaine injection causes dissociation of mGluR5-Homer2 scaffolds in striatal lysates in WT but not Homer2-AA mice. Homer2-AA mice are less sensitive to the aversive properties of high-dose cocaine under place-conditioning and taste-conditioning, indicating CaMKIIα-dependent Homer2 phosphorylation gates mGluR5 coupling and cocaine aversion. |
Homer2-AA knock-in mice (S117A/S216A), cortical neuron activity-dependent phosphorylation assay, co-immunoprecipitation of mGluR5-Homer2 from striatum, conditioned place aversion, taste conditioning |
eNeuro |
High |
36973011
|
| 2025 |
Homer2 ablation (Homer2−/− mice) causes: (1) slower insertion of nAChRs into the motor endplate and reduced nAChR activity; (2) reduced subsynaptic IP3R1 content and diminished IP3-releasable Ca²⁺; (3) impaired co-localization of CaMKIIβ with nAChRs at the endplate—demonstrating Homer2 organizes the subsynaptic microdomain coupling IP3R1 and CaMKIIβ to regulate nAChR dynamics. |
Homer2−/− transgenic mice, single-channel electrophysiology, immunofluorescence co-localization, Ca²⁺ imaging of IP3-releasable stores in isolated muscle fibers |
American journal of physiology. Cell physiology |
Medium |
41259107
|
| 2026 |
Homer2 directly binds NFATc1 in skeletal muscle, with co-immunoprecipitation showing markedly increased Homer2-NFATc1 interaction at 4 days post-injury during muscle regeneration. Homer2-positive mononuclear cells co-express myogenin, and Homer2/NFATc1 co-positive cells increase at days 4 and 6 post-injury, placing Homer2 in the calcineurin-NFAT pathway during muscle differentiation. |
Co-immunoprecipitation from regenerating tibialis anterior muscle, immunofluorescence co-localization with satellite cell (Pax7) and differentiation (myogenin) markers |
Cells, tissues, organs |
Medium |
42258588
|