SPN - sialophorin |Elisa - Clia - Antibody - Protein

Background

Sialophorin (SPN), also known as CD43, is a glycoprotein primarily expressed on the surface of immune cells, such as T lymphocytes, monocytes, neutrophils, and some B cells. SPN is involved in various aspects of immune cell function, including cell adhesion, migration, and activation. The molecule plays a critical role in modulating the interaction between immune cells and their microenvironment, particularly by regulating the adhesion properties of leukocytes, which are essential for their migration and trafficking through different tissues.

Sialophorin is a highly sialylated protein, meaning it has many sialic acid residues attached to its extracellular portion, which contribute to its negative charge. This negative charge facilitates electrostatic repulsion between cells, which can prevent adhesion in certain contexts but also enables its participation in finely tuned immune responses. SPN is an important player in the immune system's ability to differentiate between self and non-self, contributing to immune surveillance and cellular interactions during inflammatory responses.

Protein Structure

Sialophorin (CD43) is a transmembrane glycoprotein composed of 400-450 amino acids, depending on the isoform, with a molecular weight ranging between 95 to 135 kDa due to extensive post-translational modifications, including N- and O-linked glycosylation. The protein can be divided into three primary regions:

Extracellular Domain:

• The extracellular domain of SPN is large, highly glycosylated, and enriched with sialic acid residues, which give the protein its overall negative charge. This domain contains O-glycosylation sites that are critical for the protein’s function in immune cell adhesion and migration.
• Structurally, the extracellular domain extends far from the cell surface, creating a physical barrier that impacts how immune cells interact with their environment. This "mucin-like" structure is responsible for the steric hindrance and repulsive interactions between immune cells, which can regulate adhesion to endothelial cells and other immune cells.
• The glycosylation of SPN is dynamic, meaning that changes in glycosylation patterns can alter its function and the ability of immune cells to adhere to other cells or tissues. In resting immune cells, SPN maintains a highly sialylated state, promoting cell motility and limiting unnecessary adhesion. Upon activation, modifications in glycosylation can allow for increased cell-cell interactions.

Transmembrane Domain:

• The transmembrane domain is a single hydrophobic α-helix that anchors the protein in the plasma membrane. This domain provides the structural stability needed for SPN to act as a signaling receptor, facilitating the transmission of external signals to the cell's interior.
• While the transmembrane region is not directly involved in signal transduction, it allows for proper placement of the extracellular domain on the surface and interactions between the cytoplasmic domain and intracellular signaling molecules.

Cytoplasmic Domain:

• The cytoplasmic tail of SPN is relatively short, consisting of about 123 amino acids, and plays a significant role in intracellular signaling. Upon immune cell activation, the cytoplasmic domain interacts with various cytoskeletal proteins and signaling adapters.
• This interaction is crucial for mediating cellular processes such as actin cytoskeleton reorganization, migration, and signal transduction through T cell receptor (TCR) and integrins. In T lymphocytes, for example, SPN helps modulate responses to antigen presentation by influencing cytoskeletal dynamics and promoting efficient immune synapse formation.

Classification and Subtypes

Sialophorin belongs to the mucin-like glycoprotein family, a class of proteins known for their extended, heavily glycosylated extracellular domains. These proteins often serve structural and protective functions, as well as acting as receptors for cell adhesion and signaling processes.

Sialophorin itself does not have widely recognized subtypes, but its function can be modulated through alternative splicing and post-translational modifications like glycosylation. Variations in glycosylation patterns, which may be tissue-specific or activation-dependent, result in functional diversity. This functional diversity allows SPN to adapt to different immunological contexts, from maintaining cell motility to promoting immune cell activation and adhesion.

Function and Biological Significance

Sialophorin plays several crucial roles in immune function:

Immune Cell Adhesion and Repulsion:

• The primary role of SPN is to regulate the adhesive properties of immune cells. Its highly sialylated extracellular domain creates a negative charge, contributing to electrostatic repulsion between cells, which is important in preventing unintended aggregation of immune cells and promoting their ability to traffic efficiently through tissues.
• In resting immune cells, SPN promotes cell migration by limiting adhesion. However, upon immune activation, modifications in glycosylation reduce its inhibitory function and allow immune cells to adhere to target cells, such as endothelial cells, antigen-presenting cells, or sites of infection and inflammation.

Cell Migration and Trafficking:

• SPN is involved in leukocyte extravasation, the process by which immune cells migrate out of the bloodstream and into tissues in response to infection or injury. SPN's negative charge facilitates immune cell movement through the endothelial barriers by preventing adhesion under normal conditions, but when necessary, its interactions with integrins and other adhesion molecules allow cells to adhere and migrate to sites of inflammation.

T-Cell Activation and Signal Transduction:

• In T lymphocytes, SPN plays a regulatory role in TCR signaling. The cytoplasmic tail of SPN interacts with components of the cytoskeleton, including ERM (Ezrin-Radixin-Moesin) proteins, linking SPN to the actin cytoskeleton. This is essential for immune synapse formation, which allows T cells to form stable contacts with antigen-presenting cells, a critical step in antigen recognition and subsequent T-cell activation.
• SPN also influences integrin signaling, coordinating with these adhesion molecules to ensure proper immune responses are mounted in response to pathogens or damaged tissues.

Immune Evasion:

• Pathogens, particularly certain viruses and bacteria, can exploit SPN by binding to its heavily glycosylated extracellular domain. This allows pathogens to evade immune detection or modulate immune cell function to their advantage. Thus, SPN plays a dual role in immune surveillance and in providing a potential point of vulnerability to certain pathogens.

Clinical Issues

Mutations or dysregulation of SPN have been linked to various immune-related disorders, reflecting its importance in maintaining immune system balance:

Immune Deficiency:

• Aberrant expression of SPN has been associated with certain immunodeficiencies, particularly those affecting T-cell function. Defects in SPN can lead to impaired T-cell activation and signaling, resulting in weakened immune responses to infections.

Autoimmune Disorders:

• Given its role in regulating immune cell activation and adhesion, dysregulation of SPN can contribute to autoimmune diseases. For instance, improper control of cell adhesion and migration can lead to immune cells attacking healthy tissues, a hallmark of autoimmune conditions like rheumatoid arthritis or systemic lupus erythematosus (SLE).

Cancer:

• SPN expression is altered in certain types of cancers, including leukemias and lymphomas, where it plays a role in modulating cell migration, adhesion, and immune evasion by tumor cells. Altered glycosylation patterns of SPN have been observed in tumor cells, which may contribute to cancer progression by affecting the immune system’s ability to recognize and destroy malignant cells.

HIV Infection:

• SPN plays a role in HIV pathogenesis. The HIV virus exploits SPN as part of its strategy to infect T cells and evade immune detection. By binding to SPN, HIV can modulate T-cell activation and function, facilitating viral persistence and immune system evasion.

Summary

Sialophorin (SPN or CD43) is a heavily glycosylated transmembrane protein primarily expressed on the surface of immune cells. It plays crucial roles in regulating immune cell adhesion, migration, and activation. Structurally, it consists of an extended, negatively charged extracellular domain, a single transmembrane region, and a short cytoplasmic domain that mediates intracellular signaling through interactions with the actin cytoskeleton.

SPN contributes to maintaining the balance between immune cell adhesion and motility, allowing cells to navigate efficiently through tissues while preventing unnecessary aggregation. During immune activation, SPN facilitates immune synapse formation and modulates T-cell receptor signaling. Its role in immune cell migration makes it essential for proper immune surveillance and response to infections. However, dysregulation of SPN is associated with various immunodeficiencies, autoimmune diseases, cancer, and pathogen infections like HIV.

Understanding SPN’s structure and function provides insights into how immune cells interact with their environment and how defects in SPN can lead to immune-related diseases.