The ERLIN2 Knockout Raji Polyclonal Cells product is a population of human B lymphocyte-derived Raji cells that have undergone CRISPR/Cas9-mediated disruption of the ERLIN2 gene. This polyclonal knockout cell pool enables study of ERLIN2 function without selection of a single clonal genotype, preserving biological variability characteristic of heterogeneous cell populations. The loss-of-function model provides a versatile tool for dissecting ERLIN2-dependent mechanisms in a lymphoblastoid background.
The Raji cell line is a lymphoblastoid cell line derived from a Burkitt lymphoma patient and is Epstein-Barr virus (EBV)-positive. Raji cells maintain many features of mature B lymphocytes, including the capacity for antibody production and immune surveillance functions, making them a relevant model for B cell biology and hematological malignancies. Their transformed nature and viral status contribute to active lipid metabolism and ER stress pathways, which are intimately linked to the role of ERLIN2.
ERLIN2 is an ER lipid raft-associated protein that forms a complex with INSIG1 to mediate sterol-induced degradation of HMGCR, a rate-limiting enzyme in cholesterol biosynthesis. This process is transcriptionally regulated by SREBP2. In the ERAD pathway, ERLIN2 acts downstream of the ER stress sensors IRE1 and PERK, scaffolding the ubiquitin ligase AMFR/gp78 and the ATPase VCP/p97 to promote the ubiquitination and proteasomal clearance of misfolded proteins. Key downstream targets include HMGCR, LDLR, and ubiquitinated ERAD substrates. Mechanistically, ERLIN2 functions as an adaptor, facilitating the retrotranslocation and degradation of ERAD clients, and its interaction with INSIG1 couples cholesterol sensing to proteolytic control.
In Raji B lymphocytes, ERLIN2’s dual role in cholesterol homeostasis and ER proteostasis is particularly significant. The high proliferative rate of these lymphoma cells demands robust cholesterol biosynthesis for membrane biogenesis, while their immunoglobulin secretion imposes a heavy ER folding load. Disruption of ERLIN2 in this EBV-transformed background can alter lipid raft composition, impair antibody secretion, and sensitize cells to ER stress-induced apoptosis. This model thus recapitulates metabolic vulnerabilities observed in hereditary spastic paraplegia and lymphomagenesis, where ERLIN2 dysfunction has been implicated.
Researchers can employ these ERLIN2 knockout Raji polyclonal cells in diverse assays such as western blotting to assess target protein levels, RT-qPCR for gene expression analysis, flow cytometry for surface receptor profiling (e.g., LDLR), metabolic cholesterol quantification, and co-immunoprecipitation to examine the ERLIN2-INSIG1 or ERLIN2-AMFR interactions. The model supports studies on cholesterol biosynthesis regulation, ERAD efficiency, and the intersection of lipid metabolism with lymphocyte activation and oncogenic signaling. For further technical inquiries, please contact Ascent Research.
