KDEL receptor 1 CRISPR Activation Plasmid (h): sc-402751-ACT

Human KDELR1 encodes KDEL receptor 1, a Golgi-resident retrieval receptor that recognizes C-terminal KDEL-like motifs on soluble ER chaperones and mediates their retrograde transport from the Golgi to the endoplasmic reticulum via COPI-coated vesicles. By sustaining ER proteostasis and supporting the secretory pathway, KDELR1 influences ER stress signaling, unfolded protein response dynamics, and quality control of nascent proteins. Perturbation of ER–Golgi trafficking and chaperone recycling is broadly relevant to conditions characterized by secretory dysfunction and proteotoxic stress, including cancer biology, neurodegeneration, and inflammatory states. KDELR1 therefore serves as a useful node for investigating how trafficking homeostasis shapes signaling outputs and cellular fitness under stress.

KDEL receptor 1 CRISPR Activation Plasmid (h) provides a targeted, non-destructive approach to upregulating endogenous KDELR1 expression without altering the underlying DNA sequence.

KDEL receptor 1 CRISPR Activation Plasmid (h) is a three-plasmid synergistic activation mediator (SAM) system engineered for highly efficient, site-specific transcriptional upregulation of the KDELR1 locus in human cell lines. The system is built around a catalytically inactive Cas9 (dCas9) carrying two inactivating mutations (D10A and N863A) that eliminate nuclease activity while preserving DNA binding. This dCas9 is fused to VP64, a potent transcriptional activator, and is co-expressed with a blasticidin resistance gene for selection. The second plasmid encodes the MS2-p65-HSF1 fusion protein, a secondary activator complex that works in concert with dCas9-VP64, alongside a hygromycin resistance gene. The third plasmid encodes a target-specific 20 nt sgRNA fused to two MS2 RNA aptamers that recruit the MS2-p65-HSF1 complex to the activation site, accompanied by a puromycin resistance gene. The three plasmids are delivered at a 1:1:1 mass ratio for balanced expression of all system components.

Once assembled at the target locus, the SAM complex binds within approximately 200 bp upstream of the KDELR1 transcriptional start site, where VP64, p65, and HSF1 act in concert to recruit transcriptional machinery and drive upregulation of endogenous KDEL receptor 1 expression. Unlike nuclease-active Cas9, dCas9 does not introduce double-strand breaks or modify the genomic sequence, preserving the native KDELR1 locus and enabling the study of KDEL receptor 1-dependent transcriptional responses at the endogenous locus, making it a valuable tool for functional studies, target gene identification, and the modeling of KDEL receptor 1 pathway restoration in tumor cells with silenced or reduced KDELR1 expression.

For Research Use Only. Not Intended for Diagnostic or Therapeutic Use.