The HOMER1 Knockout HAP1 Polyclonal Cells comprise a polyclonal population of HAP1 cells engineered with CRISPR/Cas9-mediated disruption of the HOMER1 gene, generating a loss-of-function model for studying HOMER1-dependent signaling. This human knockout cellular model offers a renewable and genetically defined resource for investigating the scaffolding functions of HOMER1 in signal transduction pathways.
The host HAP1 cell line is a near-haploid human cell line derived from the KBM-7 chronic myeloid leukemia line. Its haploid karyotype simplifies genetic manipulation and facilitates recessive phenotype screening, making it a well-established platform for forward and reverse genetic studies. HAP1 cells retain expression of many signaling components, allowing the assessment of HOMER1??s molecular functions in a mammalian cellular context.
HOMER1 encodes a postsynaptic density scaffold protein that constitutively binds group I metabotropic glutamate receptors (mGluR1/5) and couples them to downstream effectors. Through its EVH1 domain, HOMER1 interacts with Shank family scaffold proteins, inositol 1,4,5-trisphosphate receptors (ITPR1/2/3), transient receptor potential canonical channels (TRPC1/4/5), PIKE, and dynamin-3 (DNM3), organizing a signaling complex that regulates intracellular calcium dynamics and actin cytoskeleton reorganization. HOMER1 expression is regulated by neuronal activity, CREB, BDNF, and calcium influx, and it mediates mGluR1/5 signaling to IP3R-mediated calcium release and TRPC-mediated calcium influx, as well as ERK1/2 activation. These interactions are critical for synaptic plasticity, dendritic spine morphology, and glutamatergic transmission.
Although HAP1 is not of neural origin, HOMER1 is expressed in this cell line and its disruption allows the dissection of conserved scaffold-mediated signaling mechanisms involved in calcium handling and actin remodeling. This knockout model provides a simplified cellular environment to study how loss of HOMER1 affects the coupling of mGluRs to intracellular pathways without the complexity of neuronal networks. It is particularly useful for analyzing core HOMER1 interactions with its partners and for screening potential modulators of these pathways in a high-throughput-compatible format.
Researchers can employ these polyclonal knockout cells for a range of functional studies, including calcium imaging to monitor mGluR-evoked calcium transients, co-immunoprecipitation to map altered protein?Cprotein interactions, and subcellular fractionation to assess changes in scaffolding complex assembly. The model is suitable for neuropsychiatric disease research, enabling drug screening for schizophrenia, autism spectrum disorder, and major depressive disorder, as well as for investigating synaptic plasticity mechanisms at the molecular level. Standard assays such as Western blotting, RT-qPCR, immunofluorescence, and reporter assays can be used to validate pathway perturbations. For inquiries regarding lot-specific performance or customization, please contact Ascent Research.
