The CCDC136 Knockout HeLa Polyclonal Cells product comprises a heterogeneous population of HeLa cells subjected to CRISPR/Cas9-mediated disruption of the CCDC136 gene. This polyclonal knockout model provides a genetically diverse loss-of-function system for studying CCDC136-dependent signaling pathways without clonal selection biases. The targeting strategy introduces gene inactivation across the cell pool, enabling robust functional interrogation of CCDC136 in a human epithelial cervical adenocarcinoma background.
The HeLa host cell line is derived from an HPV18-positive cervical adenocarcinoma, representing a widely used model in cancer biology and signal transduction research. HeLa cells exhibit epithelial morphology and retain key pathways of cell proliferation, ion transport, and GPCR-mediated signaling. Their robust growth characteristics and well-characterized genetic landscape make them suitable for dissecting the molecular mechanisms of ion channel regulation and its impact on cellular physiology.
CCDC136 encodes an auxiliary subunit of the NALCN sodium leak channel complex, a critical determinant of resting membrane potential. Within the channelosome, CCDC136 interacts directly with NALCN, UNC80, and UNC79 to regulate basal Na+ conductance. Upstream, M3 muscarinic receptor activation via G??q/11-coupled signaling stimulates the channel through the cAMP-PKA pathway, while downstream effectors include voltage-gated calcium channels (e.g., Cav1.2), the transcription factors CREB and c-Fos, and mitogenic signaling cascades. Disruption of CCDC136 therefore impairs GPCR-dependent sodium influx, perturbing membrane potential homeostasis and calcium-dependent transcriptional programs.
In the HeLa cervical adenocarcinoma context, loss of CCDC136 function is particularly relevant for probing the interplay between ion homeostasis and oncogenic signaling. NALCN channel activity has been implicated in cell proliferation and migration, and alterations in resting membrane potential can influence calcium dynamics and downstream mitogenic pathways. Moreover, the CCDC136 knockout model serves as a tool for neurodevelopmental disease research, as mutations in NALCN complex components are linked to intellectual disability, hypotonia, and infantile neuroaxonal dystrophy. This model thus bridges cancer cell biology and neurobiology by enabling examination of conserved channel regulatory mechanisms.
Typical research applications include electrophysiological characterization of NALCN channel properties via patch clamp, real-time monitoring of membrane potential changes using FLIPR assays, and calcium imaging with Fluo-4 to assess GPCR-stimulated responses. The polyclonal knockout cells are also suitable for western blotting to confirm target protein loss and for cell proliferation assays to evaluate the role of CCDC136 in growth control. Drug screening campaigns aimed at identifying NALCN channel modulators or compounds that restore ion homeostasis can leverage this model. For further information or to discuss custom applications, please contact Ascent Research.
