CXADR Human
Description
Molecular Structure and Isoforms
CXADR is a type I transmembrane protein with a conserved structure across mammals. Key domains include:
-
Extracellular domain (ECD): Contains two immunoglobulin-like folds (D1 and D2) responsible for homophilic adhesion and viral binding .
-
Transmembrane domain: 21-amino acid segment anchoring the protein to the membrane.
-
Intracellular domain (ICD): Interacts with cytoskeletal proteins and junctional complexes (e.g., ZO-1, microtubules) .
Table 1: CXADR Isoforms in Humans
2.1. Cell Junction Integrity
CXADR stabilizes tight junctions (TJs) and adherens junctions (AJs) in:
-
Testis: Critical for blood-testis barrier (BTB) integrity and spermatogenesis .
-
Heart: Maintains intercalated discs in cardiomyocytes; haploinsufficiency in mice leads to arrhythmias and conduction defects .
2.2. Viral Entry Mechanism
CXADR facilitates infection by:
-
Coxsackievirus B: Binds via D1 domain, enabling viral entry into cardiac and epithelial cells .
-
Adenoviruses 2/5: Viral fiber knob interacts with D1, disrupting TJs to enhance infection .
2.3. Novel Immune Role
Recent studies identify CXADR as a high-affinity Fc receptor for human IgG (KD ~1 nM), binding the Fc region competitively with anti-Fc antibodies . This links CXADR to humoral immunity and autoimmunity pathways.
Tissue Expression and Pathological Relevance
Table 2: CXADR Expression in Human Tissues
-
Cancer: CXADR loss in breast cancer correlates with PTEN/PHLPP2 downregulation, AKT activation, and poor prognosis .
-
Inflammation: Upregulated in atherosclerotic plaques (macrophages) and type 2 diabetes models (liver/heart) .
Clinical Implications
-
Cardiovascular Disease: CXADR mutations are linked to arrhythmia susceptibility post-myocardial infarction .
-
Therapeutic Target: Monoclonal antibodies (e.g., 6G10A) inhibit CXADR-mediated viral entry and tumor growth in preclinical models .
Research Advances
Product Specs
Q&A
What is the primary function of CXADR in human physiology?
CXADR functions as a cell adhesion molecule within junctional complexes, playing a pivotal role in maintaining structural integrity between epithelial cells. It is crucial for cardiac development during embryogenesis and serves as a receptor facilitating adenovirus-mediated gene transfer . Additionally, CXADR contributes to spermatogenesis by supporting Sertoli-germ cell interactions .
How is CXADR expression regulated in human tissues?
CXADR expression is regulated through transcriptional mechanisms influenced by tissue-specific factors. For instance, it is highly expressed in myocardial intercalated discs during cardiac development and localized primarily at Sertoli-Sertoli and Sertoli-germ cell interfaces in the testes . Conditional knockout models have demonstrated that its regulation is crucial for organ-specific functions .
What experimental models are used to study CXADR?
Researchers employ various models to study CXADR's functions:
-
Knockout Mouse Models: These models help elucidate the physiological roles of CXADR by observing phenotypic changes upon gene deletion .
-
Overexpression Systems: These systems are used to investigate the molecular pathways activated by CXADR.
-
In Vitro Assays: Cell culture studies enable exploration of CXADR-mediated signaling mechanisms .
What methods are available for detecting CXADR expression?
Detection methods include:
-
Western Blotting: For protein-level analysis.
-
Immunohistochemistry: To visualize spatial expression patterns.
-
Quantitative PCR: For transcriptional profiling.
How can researchers design experiments to study CXADR's role in cardiac development?
To study CXADR's role in cardiac development:
-
Employ conditional knockout mouse models targeting specific developmental stages .
-
Use RNA sequencing to analyze gene expression changes upon CXADR deletion.
-
Perform histological examinations of myocardial tissues to assess structural abnormalities .
What are the challenges of studying CXADR's role in embryonic lethality?
Embryonic lethality poses significant challenges as it prevents the study of CXADR's roles in adult tissues. Conditional knockout models circumvent this issue by allowing tissue-specific deletion at different developmental stages . Researchers can also use organoid systems or induced pluripotent stem cells (iPSCs) for functional studies.
How can contradictory data be addressed when analyzing large datasets on CXADR?
-
Use robust statistical methods to filter noise.
-
Validate findings through independent experimental replication.
-
Employ visualization tools for multidimensional data analysis .
What techniques are available for mining contradictory data related to CXADR?
Contradictory data can be mined using algorithms that enforce mutual exclusion rules within datasets:
-
Formal Concept Analysis (FCA): Visualizes contradictions by associating gene expressions with specific tissue types or developmental stages.
-
ConTra Application: Processes large datasets with high accuracy by identifying attribute values that violate predefined rules .
How can researchers ensure soundness when analyzing noisy datasets?
To ensure soundness:
-
Preprocess datasets to remove outliers and irrelevant attributes.
-
Apply machine learning algorithms capable of handling noisy inputs.
-
Validate findings through experimental corroboration using independent cohorts .
How does CXADR contribute to tumorigenesis?
CXADR contributes to tumorigenesis through its roles as an adhesion molecule and signaling mediator:
-
It facilitates cellular interactions within tumor microenvironments.
-
Monoclonal antibodies targeting CXADR have shown efficacy in inhibiting tumor growth via antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) .
-
Knockdown studies confirm that tumor progression is dependent on CXADR expression levels .
What strategies are available for developing anti-CXADR antibodies?
Antibody development strategies include:
-
Signal Sequence Trap (SST) methods for identifying membrane-bound proteins suitable as targets.
-
Screening hybridoma libraries for monoclonal antibodies with high specificity against CXADR.
-
Functional assays such as ADCC and CDC to evaluate therapeutic potential .
How can findings on CXADR be applied to immunotherapy?
CXADR-targeting antibodies represent promising candidates for cancer immunotherapy:
-
They selectively bind tumor cells expressing CXADR while sparing normal tissues.
-
Preclinical studies demonstrate their efficacy against prostate, pancreatic, and colorectal cancers .
Further evaluation of safety profiles in human tissues is necessary before clinical translation.
What are the implications of CXADR in reproductive biology?
CXADR's localization at Sertoli-Sertoli and Sertoli-germ cell interfaces underscores its importance in spermatogenesis:
Product Science Overview
CAR was first identified as a receptor for Coxsackie B viruses and Adenoviruses. The protein is composed of two extracellular domains, a transmembrane domain, and a cytoplasmic tail. The extracellular domains are responsible for binding to the viral particles, facilitating their entry into the host cell .
CAR is not only a viral receptor but also plays significant roles in normal cellular functions. It is involved in the development of the heart and the lymphatic vasculature system during embryogenesis . Additionally, CAR is implicated in maintaining the integrity of epithelial cell junctions and in the regulation of cell adhesion and signaling .
CAR serves as the primary entry point for Coxsackie B viruses and Adenoviruses. These viruses bind to the membrane-distal D1 immunoglobulin domain of CAR, which facilitates their entry into the host cell . The interaction between CAR and these viruses is a critical step in the viral life cycle, leading to various diseases such as myocarditis, conjunctivitis, gastroenteritis, pneumonia, and myocarditis .
Recombinant CAR refers to the artificially synthesized version of the CAR protein, which is used in various research and therapeutic applications. Recombinant CAR can be produced using different expression systems, including bacterial, yeast, insect, and mammalian cells. This recombinant protein is utilized in studies to understand the mechanisms of viral entry, to screen for antiviral compounds, and to develop potential therapeutic interventions .
The understanding of CAR’s role in viral infections has significant clinical implications. Targeting CAR or its interaction with viruses could lead to the development of novel antiviral therapies. Additionally, CAR’s involvement in maintaining epithelial integrity and its role in embryogenesis make it a potential target for therapeutic interventions in various diseases .
In conclusion, the Coxsackievirus and Adenovirus Receptor is a multifaceted protein with critical roles in both normal cellular functions and viral infections. The recombinant form of CAR continues to be a valuable tool in research, providing insights into viral pathogenesis and potential therapeutic strategies.
