The HOMER2 Knockout HAP1 Polyclonal Cells are a CRISPR/Cas9-edited polyclonal knockout cell population that provides a loss-of-function model for HOMER2. Derived from the HAP1 near-haploid human cell line, this product offers a genetically defined system for investigating HOMER2-dependent signaling pathways, protein interactions, and cellular processes, suitable for functional genomics, drug screening, and mechanistic studies.
The HAP1 cell line is a near-haploid human cell line derived from a chronic myeloid leukemia (CML) patient, featuring a largely haploid genome and fibroblast-like morphology. Its reduced genetic redundancy simplifies genotype?Cphenotype correlations, making it ideal for genetic screens, knockout validation, and functional studies of signal transduction, cancer biology, and cytoskeletal dynamics.
HOMER2 encodes a scaffolding protein that organizes signaling complexes by binding to group I metabotropic glutamate receptors (GRM1/mGluR1 and GRM5/mGluR5) and inositol 1,4,5-trisphosphate receptors (ITPR1/IP3R). This scaffold physically links these receptors to the actin cytoskeleton through interactions with SHANK1, DLG4 (PSD-95), Drebrin, and Filamin A. HOMER2 is activated downstream of neuronal activity, BDNF, calcium influx, CREB, and MAPK signaling, and it regulates IP3R-mediated calcium release, NF-??B transcriptional activity, and MAPK/ERK signaling. It also associates with CaMKII, influencing synaptic plasticity and actin remodeling. Knockout of HOMER2 disrupts these functions, leading to altered calcium signaling, impaired actin dynamics, and dysregulated NF-??B activation.
In HAP1 cells, HOMER2 knockout yields a uniform loss of function across the polyclonal population due to the near-haploid genome, providing a clean background to interrogate GPCR-mediated calcium signaling, cytoskeletal organization, and transcriptional responses. This model is valuable for exploring diseases associated with HOMER2, including autosomal dominant hearing loss, schizophrenia, autism spectrum disorder, and glioblastoma. The CML origin of HAP1 cells also makes it relevant for cancer research, particularly studies of NF-??B and MAPK pathways in leukemic cell survival and drug resistance.
Typical research applications include functional studies of group I mGluR signaling, high-throughput screening for modulators of calcium signaling, and investigation of actin cytoskeleton dynamics. Assays such as Western blotting, immunofluorescence for actin and mGluRs, calcium imaging, co-immunoprecipitation, NF-??B luciferase reporter assays, cell migration and proliferation assays, and drug sensitivity screening can be employed to dissect HOMER2-dependent mechanisms. These polyclonal knockout cells are suited for both mechanistic studies and genetic/pharmacological screens. For further information, please contact Ascent Research.
