F11R - F11 receptor |Elisa - Clia - Antibody - Protein

Background

The F11 receptor (F11R), also known as Junctional Adhesion Molecule-A (JAM-A), is an integral protein involved in cell-cell adhesion, particularly in the tight junctions of epithelial and endothelial cells. It belongs to the immunoglobulin superfamily and is vital for maintaining barrier integrity in tissues where selective permeability is essential, such as blood-brain, blood-testis, and blood-retina barriers. F11R plays a key role in regulating paracellular permeability, leukocyte transmigration, and cellular signaling, supporting immune responses, hemostasis, and wound healing. It also mediates interactions between platelets, contributing to thrombus formation and platelet aggregation.

Expressed in a variety of tissues, including the endothelium, epithelium, and on platelets, F11R facilitates cell adhesion and communication in multiple physiological processes. Notably, it has been implicated in pathological conditions like inflammation, atherosclerosis, and cancer metastasis, where its dysregulation disrupts cellular integrity and promotes disease progression.

Protein Structure

The F11R protein is a type I transmembrane protein and has a complex structure with well-defined domains responsible for its interactions and functions:

Extracellular Domain:

• The extracellular region of F11R contains two immunoglobulin-like (Ig-like) domains: an N-terminal V-type and a C2-type domain. These domains are crucial for its adhesive properties, allowing F11R to interact homotypically (binding with another F11R molecule on adjacent cells) or heterotypically (interacting with other proteins on leukocytes and platelets).
• The Ig-like domains form the primary binding sites for the interaction with other F11R molecules on adjacent cells, supporting tight junction assembly and cellular adhesion.
• This region also has glycosylation sites that stabilize the protein and contribute to proper folding and function.

Transmembrane Domain:

• The single transmembrane domain spans the cell membrane, anchoring F11R in place and playing a role in signal transduction. This domain allows F11R to participate in both intracellular signaling and extracellular interactions critical for cell adhesion.

Cytoplasmic Tail:

• The cytoplasmic tail of F11R contains motifs for binding to cytosolic proteins and interactions with the cytoskeleton. This region interacts with signaling molecules such as zona occludens proteins (ZO-1) and the actin cytoskeleton, facilitating tight junction assembly and intracellular signaling pathways.
• Phosphorylation sites within the cytoplasmic domain regulate F11R’s adhesion and signaling functions, modulating its role in cellular junctions and response to cellular stress or injury.

Classification and Subtypes

F11R is classified within the immunoglobulin superfamily due to its Ig-like domains. As a member of the junctional adhesion molecule (JAM) family, it is sometimes referred to as JAM-A, distinguishing it from other members, such as JAM-B and JAM-C. JAM family members generally share structural similarities, with conserved Ig domains that support adhesive functions, but each member also has unique roles in specific tissues or cell types. F11R (JAM-A) is specifically involved in epithelial and endothelial barrier functions and platelet aggregation, while other JAM family members play more specialized roles in immune cell trafficking or vascular development.

Function and Biological Significance

The primary functions of F11R include cell-cell adhesion, maintenance of tight junctions, and regulation of paracellular permeability. These functions are crucial for maintaining epithelial and endothelial barriers in tissues that require selective permeability, contributing to immune responses and maintaining cellular integrity:

Tight Junction Formation and Maintenance:

• F11R is critical in forming tight junctions, which control the paracellular movement of ions and molecules across epithelial and endothelial barriers. In endothelial cells, F11R helps prevent unregulated passage of solutes and immune cells, maintaining tissue homeostasis and protecting against pathogens.
• It interacts with other junctional proteins such as ZO-1, occludin, and claudins, reinforcing the tight junction structure and ensuring its stability.

Regulation of Paracellular Permeability:

• By mediating cell-cell adhesion, F11R plays a key role in controlling the selective permeability of epithelial and endothelial barriers, which is crucial for maintaining tissue environments. In response to inflammatory signals, F11R expression may change, altering the permeability of endothelial barriers and facilitating leukocyte migration into tissues during immune responses.

Role in Leukocyte Transmigration:

• F11R is involved in leukocyte transmigration across the endothelium, a process essential for immune surveillance and response. It interacts with integrins and other adhesion molecules on leukocytes, guiding them across endothelial barriers into tissues where they combat infection or injury.

Platelet Aggregation and Thrombosis:

• On platelets, F11R facilitates aggregation and thrombus formation through interactions with platelet adhesion molecules. It acts as a receptor for homophilic interactions, allowing platelets to adhere to each other in response to vascular injury, which is essential for wound healing and hemostasis.

Signal Transduction:

• Through its interactions with cytosolic proteins and the cytoskeleton, F11R participates in intracellular signaling pathways that respond to stress, inflammation, and cellular damage. Its ability to interact with signaling molecules helps cells modulate their response to environmental changes and maintain barrier integrity.

Clinical Issues

Dysregulation of F11R has been associated with several pathological conditions, including inflammatory diseases, cardiovascular disorders, and cancer:

Inflammation and Autoimmune Diseases:

• Aberrant F11R expression can lead to increased vascular permeability and leukocyte migration, contributing to inflammation. Elevated F11R levels have been observed in diseases like rheumatoid arthritis, inflammatory bowel disease, and multiple sclerosis, where it may exacerbate inflammatory processes by allowing immune cells to infiltrate tissues excessively.

Atherosclerosis and Cardiovascular Disease:

• F11R is implicated in the development of atherosclerosis, where its role in endothelial barrier regulation and leukocyte adhesion promotes the accumulation of inflammatory cells in blood vessel walls. This accumulation contributes to plaque formation and the progression of cardiovascular disease. F11R is also involved in platelet aggregation, linking it to thrombus formation, which can lead to heart attacks and strokes if blood flow is obstructed.

Cancer Metastasis:

• F11R expression has been associated with the metastatic potential of certain cancers. By altering cell adhesion properties and enabling cancer cells to penetrate endothelial barriers, F11R facilitates the spread of cancer cells from the primary tumor site to distant organs. Its expression in tumor microenvironments can also enhance tumor vascularization, supporting cancer growth and spread.

Infectious Diseases:

• In some infectious diseases, pathogens exploit F11R to invade or compromise epithelial barriers, aiding their spread and persistence. Dysregulation or manipulation of F11R by pathogens can weaken epithelial and endothelial barriers, facilitating pathogen dissemination.

Summary

The F11R (JAM-A) protein is a type I transmembrane protein belonging to the immunoglobulin superfamily. Characterized by two extracellular Ig-like domains, a transmembrane segment, and a cytoplasmic tail, F11R is critical for cell-cell adhesion in epithelial and endothelial tissues. It functions primarily to maintain tight junction integrity, regulate paracellular permeability, and support immune cell transmigration. Additionally, it plays a role in platelet aggregation and thrombus formation, making it essential for vascular homeostasis and hemostasis.

Clinically, F11R is involved in several disorders, including inflammatory and autoimmune diseases, cardiovascular diseases like atherosclerosis, and cancer metastasis. Its role in maintaining endothelial integrity and regulating immune cell infiltration makes it a promising therapeutic target for managing these conditions. Moreover, as a mediator of platelet aggregation, F11R is a potential target in developing treatments for thrombosis and other cardiovascular complications. The study of F11R provides insights into cellular adhesion mechanisms and its role in disease pathology, with ongoing research focused on therapeutic interventions that modulate its function for disease management.