PCDH19 Antibodies

Background

The PCDH19 gene is located on the X chromosome and encodes protocadherin 19, a transmembrane protein that plays a key role in adhesion and signal transduction between neuronal cell membranes. This gene mainly regulates the assembly and function of neural networks by maintaining the normal arrangement of neurons and the stability of synaptic connections during brain development. When this gene mutates, even if there are normal alleles, it will cause PCDH19-related epilepsy due to the unique "cell interference" mechanism, mainly manifested as early-onset epilepsy in women, cognitive impairment and behavioral abnormalities. Since its first discovery of its association with epilepsy in 2008, as one of the few X-linked genes showing a special dominant inheritance pattern, its unique pathogenic mechanism has provided an important model for studying the molecular basis, gender-specific expression and neurodevelopmental disorders of epilepsy, promoting breakthroughs in the understanding of the formation and abnormal mechanisms of brain neural networks.

Structure Function Application Advantage Our Products

Structure of PCDH19

PCDH19 is a transmembrane protein with a molecular weight of approximately 100 kDa. This value varies slightly among different mammals due to splicing variants and the degree of glycosylation modification.

Species	Human	Mouse	Bovine
Molecular Weight (kDa)	100	98	101
Primary Structural Differences	With six extracellular calcium mucins repetitive structure domain	Intracellular period is shorter, the lack of part of the control sequence	Amino acids in the transmembrane region are highly conserved

The extracellular segment of this protein is composed of six cadherin repeat domains (EC1-EC6) as its core framework, which form specific homologous affinity binding through a calcium ion-dependent mechanism. Its intracellular segment contains conserved signal motifs that can recruit intracellular adaptor proteins to jointly regulate the adhesion junctions and signal transduction between neurons. This structural feature shows significant evolutionary conservation across different species, especially maintaining a high degree of consistency in calcium ion-binding pockets and cell recognition interfaces.

Fig. 1:PCDH19 variants in mosaic male patients with PCDH19-related epilepsy. Fig. 1 PCDH19 variants in mosaic male patients with PCDH19-related epilepsy.¹

Key structural properties of PCDH19:

Extracellular calcium section contains six mucins repetitive structure domain (EC1 - EC6)
Calcium ion binding sites mediate homophilic interaction
Highly conservative intracellular segment assembly cell signaling and regulation for conduction neural network

Functions of PCDH19

The core function of the PCDH19 gene is to mediate the adhesion and recognition between neurons to regulate brain development. However, it is also involved in a variety of neurophysiological processes, including neural network assembly and the occurrence of epilepsy.

Function	Description
Cell adhesion	The specific recognition and adhesion between neurons are mediated through calcium ion-dependent homophils to ensure the correct spatial arrangement of neurons.
Synaptic formation	Participate in the construction and maintenance of excitatory synapses, and regulate presynaptic differentiation and the assembly of postsynaptic signal complexes.
Neural network assembly	Selective cell adhesion guides specific groups of neurons to form functional networks, supporting inter-brain information processing.
Regulation of epilepsy occurrence	Gene mutations disrupt the normal assembly of neuronal circuits and induce gender-specific epileptic seizures through a "cell interference" mechanism.
The influence of neural plasticity	Participate in dendritic spines form adjustment, affect learning and memory neural circuits associated plasticity.

Pcdh19-mediated cell recognition exhibits molecular specificity, which is different from the extensive adhesion of classical cadherins. Its selective interactions form the structural basis for the fine assembly of neural circuits, and this characteristic is of great significance for understanding brain development and disease mechanisms.

Applications of PCDH19 and PCDH19 Antibody in Literature

1. Borghi, Rossella, et al. "Modeling PCDH19-CE: From 2D Stem Cell Model to 3D Brain Organoids." International Journal of Molecular Sciences 23.7 (2022): 3506. https://doi.org/10.3390/ijms23073506

The article indicates that PCDH19 cluster epilepsy is a hereditary disease. Currently, its pathogenic mechanism is still unclear and there is a lack of effective therapy. Traditional animal models are difficult to simulate human phenotypes, while brain organoids constructed based on iPSC technology provide a new approach for studying the role and pathological mechanism of PCDH19 in neural development in a three-dimensional environment.

2. Moncayo, Juan A., et al. "Adjuvant treatment for protocadherin 19 (PCDH19) syndrome." Cureus 14.7 (2022): e27154. https://doi.org/10.7759/cureus.27154

The article indicates that PCDH19 syndrome mainly affects women and there is currently no standard treatment. Literature reviews show that chlorobarazan and bromides can reduce seizures by half. The ketogenic diet has potential for refractory epilepsy in young children. Seltepentanol has achieved long-term seizory-free status in some individual cases, but most therapies still need further validation.

3. Pancho, Anna, et al. "Modifying PCDH19 levels affects cortical interneuron migration." Frontiers in Neuroscience 16 (2022): 887478. https://doi.org/10.3389/fnins.2022.887478

The article indicates that PCDH19 is a transmembrane protein encoded by the X chromosome, and its abnormal function can cause epilepsy. This study focused on cortical interneurons and found that the dose balance of PCDH19 is crucial for their migration. Altering the expression level of PCDH19 can interfere with neuronal movement, and its intracellular and extracellular domains have different functions, indicating that PCDH19 regulates brain development through complex mechanisms.

4. Moncayo, Juan A., et al. "Understanding protein protocadherin-19 (Pcdh19) Syndrome: a literature review of the pathophysiology." Cureus 14.6 (2022). https://doi.org/10.7759/cureus.25808

The article indicates that PCDH19 syndrome is a single-gene epilepsy related to the PCDH19 gene. The pathogenesis of this disease remains unclear. Four main hypotheses have been proposed in existing studies: GABA(A) receptor dysfunction, blood-brain barrier dysfunction, cellular interference mechanisms, and abnormal neurosteroid metabolism caused by defects in AKR1C1-3 gene products.

5. Chouery, Eliane, et al. "PCDH19 in males: are hemizygous variants linked to autism?." Genes 14.3 (2023): 598. https://doi.org/10.3390/genes14030598

In this study, a new hemizygous variation of the PCDH19 gene was identified in two male children with autism spectrum disorder (ASD) but no epilepsy. This discovery expands the clinical phenotype of PCDH19, indicating that this gene may independently be involved in the pathogenesis of autism.

Creative Biolabs: PCDH19 Antibodies for Research

Creative Biolabs specializes in the production of high-quality PCDH19 antibodies for research and industrial applications. Our portfolio includes monoclonal antibodies tailored for ELISA, Flow Cytometry, Western blot, immunohistochemistry, and other diagnostic methodologies.

Custom PCDH19 Antibody Development: Tailor-made solutions to meet specific research requirements.
Bulk Production: Large-scale antibody manufacturing for industry partners.
Technical Support: Expert consultation for protocol optimization and troubleshooting.
Aliquoting Services: Conveniently sized aliquots for long-term storage and consistent experimental outcomes.

For more details on our PCDH19 antibodies, custom preparations, or technical support, contact us at email.

Reference

Chen, Yi, et al. "PCDH19-related epilepsy in mosaic males: the phenotypic implication of genotype and variant allele frequency." Frontiers in Neurology 13 (2022): 1041509. https://doi.org/10.3389/fneur.2022.1041509