PARD3 - Partitioning Defective 3 Homolog | Elisa - Clia - Antibody - Protein

Background

Partitioning defective 3 homolog (PARD3) is a key scaffolding protein involved in the establishment and maintenance of cell polarity. Originally identified in the model organism Caenorhabditis elegans, PARD3 has since been found to play crucial roles in various cellular processes in mammals, including asymmetric cell division, epithelial cell polarity, and neuronal development. PARD3 functions as part of the Par complex, which also includes PARD6 and atypical protein kinase C (aPKC). This complex is essential for the spatial organization of cellular components, enabling cells to carry out specialized functions.

Protein Structure

PARD3 is characterized by several functional domains that facilitate its role as a scaffolding protein:

• N-terminal PDZ Domains (PDZ1, PDZ2, PDZ3): These domains mediate protein-protein interactions, allowing PARD3 to bind to various partners, including other components of the Par complex and cell polarity proteins.
• CR1 (Coiled-Coil Region 1): This region is involved in the homodimerization of PARD3, essential for its function in cell polarity.
• CR3 (Coiled-Coil Region 3) / aPKC Binding Site: This domain mediates interactions with aPKC, anchoring the Par complex to specific cellular locations.
• C-terminal Region: Contains additional interaction motifs and domains that facilitate binding to other polarity proteins and signaling molecules.

Classification and Subtypes

PARD3 belongs to the PAR (Partitioning defective) protein family, which includes:

• PARD3A: The most commonly studied isoform, involved in epithelial cell polarity and asymmetric cell division.
• PARD3B: Another isoform with overlapping but distinct functions, potentially involved in specific tissue or developmental contexts.

Function and Biological Significance

PARD3 is integral to various cellular and developmental processes:

• Cell Polarity: PARD3 is crucial for the establishment of apical-basal polarity in epithelial cells, organizing the spatial distribution of membrane proteins and cytoskeletal elements.
• Asymmetric Cell Division: By regulating the orientation of the mitotic spindle and the distribution of cell fate determinants, PARD3 ensures asymmetric division, essential for stem cell function and tissue development.
• Neuronal Development: PARD3 plays a key role in the polarization of neurons, influencing axon-dendrite specification and synapse formation.
• Tight Junction Formation: PARD3 is involved in the formation and maintenance of tight junctions in epithelial cells, which are essential for barrier function and cell-cell adhesion.

Clinical Issues

Dysregulation or mutations in PARD3 are associated with several diseases:

• Cancer: Aberrant expression or mutations of PARD3 can disrupt cell polarity and contribute to tumorigenesis and metastasis. Loss of polarity is a hallmark of epithelial-to-mesenchymal transition (EMT), a process involved in cancer progression.
• Neurological Disorders: Given its role in neuronal polarity and synapse formation, mutations in PARD3 may be implicated in neurodevelopmental disorders and neurodegenerative diseases.
• Kidney Diseases: PARD3 is essential for the function of renal epithelial cells. Dysregulation can contribute to renal pathologies, including polycystic kidney disease and chronic kidney disease.

Summary

Partitioning defective 3 homolog (PARD3) is a crucial scaffolding protein that plays a key role in establishing and maintaining cell polarity. Structurally, PARD3 features multiple PDZ domains for protein interactions, coiled-coil regions for dimerization and binding to aPKC, and additional motifs for interacting with other polarity proteins. PARD3 is integral to processes such as epithelial cell polarity, asymmetric cell division, neuronal development, and tight junction formation. Dysregulation of PARD3 is associated with cancer, neurological disorders, and kidney diseases. Understanding the functions and mechanisms of PARD3 in cellular polarity provides insights into its potential as a therapeutic target for these conditions.