BST1 - bone marrow stromal cell antigen 1 |Elisa - Clia - Antibody - Protein

Background

BST1, also known as bone marrow stromal cell antigen 1 or CD157, is a multifunctional glycoprotein involved in immune signaling, cell adhesion, and calcium signaling. BST1 is part of the ADP-ribosyl cyclase family, which also includes CD38, another NAD-glycohydrolase enzyme involved in immune and calcium signaling. It is encoded by the BST1 gene located on chromosome 4p15 in humans and is predominantly expressed in bone marrow stromal cells, but also in peripheral immune cells, endothelial cells, and various tissues with immune functions. BST1 is also identified as a GPI (glycosylphosphatidylinositol)-anchored protein, which enables it to be tethered to cell membranes, facilitating cell-cell interactions and intracellular signaling. This protein is highly relevant in immunology, given its involvement in cellular processes associated with immune responses and inflammation.

Protein Structure

BST1 is a GPI-anchored cell surface protein with a molecular weight of approximately 45-50 kDa. Its structure is characterized by several distinct features:

Extracellular Domain:

• The majority of the protein's structure is extracellular and consists of a central NAD+-binding domain that catalyzes the conversion of NAD+ into cyclic ADP-ribose (cADPR) and ADP-ribose. This enzymatic activity is essential for calcium signaling.
• BST1 possesses a characteristic globular structure that facilitates its interaction with other cell surface proteins and ligands, notably CD38 and other adhesion molecules.
• The extracellular domain also includes glycosylation sites that help stabilize BST1 on the cell membrane and enhance its interaction with other immune cells.

Glycosylphosphatidylinositol (GPI)-Anchor:

• BST1 is attached to the cell membrane via a GPI anchor, a post-translational modification that provides membrane localization without transmembrane spanning domains.
• The GPI anchor allows BST1 to be positioned on lipid rafts, regions in the membrane enriched with signaling molecules. This positioning facilitates interactions with other cell surface receptors and cytoplasmic signaling proteins.

N-terminal and C-terminal Domains:

• The N-terminal and C-terminal regions contribute to the structural stability of BST1. While the N-terminal domain facilitates initial attachment to the cell membrane, the C-terminal domain interacts with adjacent cell surface molecules to regulate intracellular signaling.

Classification and Subtypes

BST1 belongs to the ADP-ribosyl cyclase family, a group of enzymes that regulate calcium signaling through NAD+ metabolism. This family includes CD38, which also has ADP-ribosyl cyclase and NADase activities. However, unlike CD38, BST1 lacks clearly defined isoforms or subtypes in humans. While it shares functional similarities with CD38, BST1’s expression pattern and regulatory mechanisms are distinct, underscoring its unique roles in immune modulation.

Function and Biological Significance

BST1 functions primarily as an immune modulator, mediating a variety of immune responses and facilitating cell adhesion and signaling. Its roles are broad and have been linked to immune regulation, inflammation, and bone marrow cell interactions.

Calcium Signaling and NAD+ Metabolism:

• BST1 catalyzes the conversion of NAD+ to cyclic ADP-ribose (cADPR), a potent calcium-mobilizing agent. Calcium signaling is vital in numerous cellular processes, including cell proliferation, apoptosis, and immune cell activation.
• Through its NADase activity, BST1 plays an important role in controlling intracellular calcium levels, especially in immune cells such as monocytes, neutrophils, and macrophages, which are essential for immune responses.

Immune Cell Adhesion and Migration:

• BST1 promotes cell adhesion and migration by binding to specific ligands and interacting with other immune receptors. Its expression on stromal cells in bone marrow aids in the adhesion of hematopoietic stem cells, thus regulating their mobilization and migration.
• It is also involved in the recruitment and movement of leukocytes to sites of infection and inflammation, partly through its interactions with integrins and adhesion molecules, further underscoring its role in immune regulation.

Role in Inflammation and Immunity:

• BST1 is upregulated in response to inflammatory stimuli, such as cytokines and infection, which triggers an increase in its NADase activity and contributes to cellular activation and immune responses.
• In diseases such as rheumatoid arthritis and various cancers, BST1 is overexpressed, and this upregulation is thought to support chronic inflammatory responses, potentially contributing to disease progression.

Tumor Microenvironment and Immune Evasion:

• BST1 expression in certain tumors aids in immune evasion by influencing immune checkpoints and promoting an immunosuppressive environment. Its interactions with other immune-modulatory molecules can inhibit T cell activation, allowing tumor cells to escape immune surveillance.

Clinical Issues

BST1 has been linked to several diseases, most notably chronic inflammatory conditions and certain cancers. Its role in immune regulation and inflammation has made it a focus of research in both diagnostic and therapeutic applications.

Cancer:

• BST1 expression has been identified in multiple types of cancer, including breast cancer, colorectal cancer, and lymphoma, and is thought to contribute to immune evasion in the tumor microenvironment.
• High BST1 expression is associated with poor prognosis in some cancers, as it can suppress immune cell activity and promote tumor growth. Targeting BST1 to improve immune responses is being explored as a potential therapeutic strategy.

Chronic Inflammatory Diseases:

• In rheumatoid arthritis (RA) and other autoimmune diseases, BST1 expression on monocytes and synovial cells is elevated, correlating with disease severity. This increase in BST1 expression may exacerbate inflammation and promote immune cell recruitment to affected tissues.
• Strategies to reduce BST1 activity or block its interactions with immune cells could help reduce inflammation and alleviate symptoms in RA and other inflammatory conditions.

Potential for Targeted Therapies:

• Given its role in immune modulation, BST1 is being studied as a target for immune-based therapies, particularly in cancer and chronic inflammation.
• Immunotherapies that block BST1’s enzymatic function or its interactions with immune cells are under development, with the aim of enhancing immune responses and preventing immune cell exhaustion in both cancer and autoimmune diseases.

Summary

BST1, or CD157, is a GPI-anchored glycoprotein and member of the ADP-ribosyl cyclase family that functions as an immune modulator, primarily through NAD+ metabolism and calcium signaling. Structurally, BST1 has a large extracellular domain with NAD+-binding capability and is anchored to the membrane via a GPI linkage, enabling interactions with other cell surface receptors. BST1’s main roles include facilitating cell adhesion, modulating calcium signaling, and supporting immune responses, particularly in inflammatory environments. Clinically, BST1 is implicated in chronic inflammatory diseases and cancers, where its expression can promote immune suppression and immune cell recruitment, contributing to disease progression. As a result, BST1 is being investigated as a target for therapeutic intervention in cancer and autoimmune diseases. Its unique role in immune modulation continues to make it a valuable focus for research aimed at developing new strategies to manage inflammation, immune regulation, and immune checkpoint control.