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DNER

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All listed services and products are For Research Use Only. Do Not use in any diagnostic or therapeutic applications.

Background

Delta/Notch-like epidermal growth factor-related receptor (DNER) is a single-pass type I transmembrane protein of 737 amino acids length with an estimated size of 82.5 kDa. The protein structure consists of an extracellular domain with ten tandem epidermal growth factor (EGF)-like repeats which are structurally related to similar domains in the Notch receptor family and bona-fide canonical Notch ligands including Delta and Jagged, followed by single transmembrane domain and short cytoplasmic tail. Unlike classical Notch ligands, DNER has lost the DSL binding domain but still binds to Notch receptors through its first and second EGF-like repeats to activate both canonical CSL-dependent and non-canonical Deltex-dependent signaling pathways. The DNER is mainly expressed in the nervous system with high expression levels in developing and adult cerebellum (especially Purkinje neurons), pyramidal neurons of the hippocampus, mitral cells of the olfactory bulb; spiral ganglion neurons and inner ear hair cells. Thus, this protein is specifically found in dendritic membranes, early endosomes and the plasma membrane, making it a key mediator during astrocytogenesis and Bergmann glial maturation. In addition to its neurodevelopmental functions, DNER is also being discovered as the target antigen of anti-Tr autoantibodies in paraneoplastic cerebellar degeneration associated with Hodgkin lymphoma and involved in cancer stemness conferring properties, prostate cancer progression and glucose homeostasis generator of pancreatic beta-cells. Moreover, genome-wide association studies have additionally implicated DNER as a susceptibility locus for type 2 diabetes and pulmonary function, emphasizing its extensive biomedical significance.

Fig.1 Association of DNER expression with various diseases. (OA Literature)Fig.1 Association of DNER expression with various clinicopathological parameters and survival probability in gastric cancer.1

DNER Protein Function: Orchestrating Neural Circuit Formation and Beyond

With molecular synergies reflecting versatile actions, the functional landscape of DNER spans the domains of neurodevelopment, neuroimmunology and oncology:

  • Neuron-Glia Communication and Astrocytogenesis: DNER mediates crucial intercellular communication between neurons and glial cells in CNS development. DNER on the dendrites of Purkinje neurons activates Notch in neighboring Bergmann glia, leading to morphological maturation, process extension, and functional polarization. While DNER-deficient mice do not survive until adulthood, they exhibit delayed cerebellar maturation and motor coordination deficits, as well as impaired glutamate clearance from synapses, providing evidence of the irreplaceable role that this protein plays in neuronal circuit formation.
  • Neuronal Polarity and Synaptogenesis: DNER regulates development in spiral ganglion neurons (SGN) of the inner ear, controlling Notch-dependent regulation of dendritic polarity, neurite length and synapse formation. Silencing DNER alters SGC polarity, dendritic length, α-synuclein expression and AMPA receptor GluR2/3 subunit expression in SGNs suggesting the importance of DNER for establishing auditory neural connectivity and pathophysiology of sensorineural hearing loss.
  • Paraneoplastic Neurology and Autoimmune Cerebellar Ataxia: DNER was detected as the onco-target antigen of anti-Tr, the serological signature antibody found in paraneoplastic cerebellar degeneration PCD associated with Hodgkin lymphoma. Anti-Tr/DNER antibodies target specifically the extracellular domain of DNER on Purkinje cell dendrites, and their detection by standardized recombinant cell-based assays has a sensitivity 100% specificity, thus making anti-DNER reagents invaluable for diagnostic immunology as well as mechanistic studies of antibody-mediated neurodegeneration.

DNER Membrane Protein Product

Creative Biolabs provides DNER membrane protein products to support structural and functional studies of this neuron-associated signaling receptor. Our membrane protein platform offers DNER constructs and preparations suitable for a range of research applications. Available products may include membrane-associated proteins or extracellular-domain constructs for structural studies, binding assays, antibody development and characterization, and investigations of DNER-related signaling and neuron–glia interactions. Product format, expression strategy, and functional characterization should be determined according to the specific product data and intended research application.

DNER Protein Product

Not finding the protein product you need? Contact us to start your one-stop custom service!

DNER Stable Cell Line Product

Creative Biolabs offers custom-engineered DNER membrane protein stable cell lines with consistently high levels of target DNER expression. These stable cell lines will be useful for drug screening, ligand binding, Notch reporter assay, paraneoplastic antibody detection and high throughput screening as a reproducible tool to study DNER biology or pharmacology. Our science also ensures great expression and cell health, allowing you to move through your research pipeline faster. To study the Notch activation and neuron-glia interaction mechanisms, we provide DNER-overexpressing lines; we also have DNER-knockdown lines for loss-of-function studies that were validated by flow cytometry, Western blotting and functional Notch reporter assays. CSL-dependent luciferase or Deltex-dependent morphological readouts in specialized reporter cell lines with therapeutically relevant properties allow real-time monitoring of both canonical and non-canonical Notch signaling, making these powerful systems for therapeutic screening and mechanistic studies.

DNER Stable Cell Line Product

Not finding the stable cell line product you need? Contact us to start your one-stop custom service!

DNER Recombinant Antibody Product

Our provision a full range of high-affinity recombinant antibodies to DNER, which are designed under the higher standard for diverse research applications. Produced using modern recombinant technologies, these antibodies are far superior in their specificity and sensitivity, with a good degree of batch to batch consistency when compared with traditional polyclonal antibodies. Please follow the links provided to view the complete list of validated products that we have available for DNER detection in whole tissues, cells or cell extracts (cerebellar tissue sections, serum, cerebrospinal fluid/CSF and cell lysates respectively) and assays such as Western Blotting (WB), ELISA, Flow Cytometry (FCM), Immunofluorescence (IF), Immunocytochemistry (ICC), Immunohistochemistry (IHC) and Immunoprecipitation(IP). The antibodies can be ordered recognizing different DNER epitopes, including glycosylation dependent epitopes mirroring those recognized by patient anti-Tr antibodies, the cytoplasmic tails (CT) approximating the studies on cellular localizations and extracellular domains (ECD), which are useful for assessing paraneoplastic antibody development and binding of Notch ligands; thus comprehensively analyzing DNER in health, disease and autoimmunity.

DNER Recombinant Antibody Product

Not finding the recombinant antibody product you need? Contact us to start your one-stop custom service!

Product Features

  • High Purity & Activity: High purity and verified integrity for dependable downstream work.
  • Diverse Expression Systems: Choice of expression formats to match routine or specialized projects.
  • Species Reactivity: Products available for human, mouse, pig, and other species.
  • Validated Applications: Application-tested to deliver consistent signals across common lab workflows.
  • Exceptional Lot-to-Lot Consistency: Tight lot-to-lot control for reproducible performance.
  • Customization Options: Flexible customization of tags, labels, or packaging upon request.

Custom DNER Membrane Protein and Antibody Discovery Services

In addition to our portfolio products, Creative Biolabs provides specialized custom services in membrane protein and antibody discovery & development. With years of experience and fully updated platforms, we can support you with:

  • Custom DNER Receptor Production: Tailored expression, purification, and characterization of challenging multi-domain receptor constructs.
  • Custom Antibody Development: From antigen design to antibody engineering (monoclonal, polyclonal, recombinant) for specific research applications.
  • Stable Cell Line Development: Generation of bespoke stable cell lines expressing your target of interest.
  • Functional Assay Development: Designing and executing assays to assess receptor activation and ligand.

Frequently Asked Questions (FAQ)

  1. What DNER products of Creative Biolabs available?

    Recombinant DNER membrane proteins in VLP, mammalian membrane extracts, ECD-Fc fusions; stable cell line expressing DNER (overexpressing and Notch reporter lines) high-affinity recombinant DNER antibodies targeting different epitopes (extracellular domain, cytoplasmic tail, glycosylation-dependent) protein engineering & antibody discovery services fully customizable. Products exist for human, mouse, rat as well as other mammalian species.

  2. Can your anti-DNER antibodies work for immunofluorescence staining of paraformaldehyde-fixed cerebellar cortex/molecular layer/granule cell layer sections in mapping distribution of Bergmann glia process and parallel fibers?

    Yes, chosen clones have been confirmed on lightly fixed cerebellar cryosections and archival paraffin-embedded specimens after antigen retrieval with specific staining along Bergmann glia radial fibers and granule cell dendritic claws that overlap with known glial and synaptic markers. This validation consisted of competition with individual peptides, absorption of ectodomain-shed fragments and controls with recombinant antigens to confirm specificity within complex distributions of native neural tissues.

  3. Is your recombinant DNER ectodomain offered in a carrier-free format that maintains calcium-dependent EGF-repeat conformation and is ready for use in Notch-binding kinetics, bead-based capture or oligomerization studies?

    Yes, the protein is a highly concentrated defined calcium containing buffer at physiological pH and free of carrier proteins, or chelating agents, and monitored for endotoxins. It allows for direct dilution into bio-layer interferometry reactions, amine-coupling to biosensor chips, or oligomerization assays without the need for dialysis or intermediary buffer exchanges and preserves the disulfide-linked EGF-repeat structure required for Notch-binding.

  4. Are your DNER reagents specifically for clinical diagnostic testing of cerebellar ataxias and neurodevelopmental delay screening or profiling patient mutations?

    No, all reagents and service provided are for research use only and not for diagnostics or therapeutic purposes.

Reference
  1. To, Han Thi Ngoc, et al. "Delta/notch-like epidermal growth factor-related receptor (DNER), a potential prognostic marker of gastric cancer regulates cell survival and cell cycle progression." International Journal of Molecular Sciences 24.12 (2023): 10077. Under Open Access license CC BY 4.0, without modification. https://doi.org/10.3390/ijms241210077
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