Cell surface proteins are molecules embedded within a cell’s outer membrane, acting as communication hubs that allow cells to interact with their surroundings and each other. These proteins are fundamental for biological processes, including receiving signals, transporting substances, and maintaining cell structure. CD157 is one such protein, recognized for its diverse roles in normal bodily functions and disease states. Understanding CD157 offers insights into cellular communication and potential medical advancements.
Understanding CD157
CD157 is a cell surface glycoprotein, also known as bone marrow stromal antigen 1 (BST-1). It belongs to the ADP-ribosyl cyclase family of enzymes, which also includes CD38, its paralog. Both CD157 and CD38 are located on chromosome 4 in humans.
CD157 functions as an ectoenzyme, meaning it performs its enzymatic activity on the outer surface of cells. This molecule exhibits about 33% similarity in its amino acid sequence with CD38. While both CD157 and CD38 are involved in catalyzing reactions that produce cyclic ADP-ribose (cADPR) from NAD+, CD157 is considered a weaker catalyst than CD38.
Where CD157 Resides in the Body
CD157 is broadly distributed throughout the body. It is found on various cell types, including hematopoietic stem cells, which generate all blood cell types. Myeloid cells, a type of white blood cell, also express CD157.
Endothelial cells, which line blood vessels, also possess CD157, particularly in brain microvessels. Specific neuronal populations in the brain, including cells in the ventricular and subventricular zones, express CD157. Its presence in the gut and lymphoid tissue is also notable.
The Multifaceted Functions of CD157
CD157’s enzymatic activity leads to the production of cyclic ADP-ribose (cADPR). cADPR is an intracellular messenger that regulates calcium levels within cells. This calcium signaling is fundamental for numerous cellular processes, including muscle contraction, nerve impulse transmission, and immune responses.
Beyond its enzymatic role, CD157 is involved in cell adhesion and cell-cell communication. It can bind with high affinity to heparin binding domains found within fibronectin and other extracellular matrix (ECM) components. This binding allows CD157 to act as an adhesion protein, forming a complex with integrins and initiating intracellular signals.
These interactions are crucial for processes like leukocyte trafficking, which involves the controlled migration of immune cells. CD157 facilitates the adhesion of leukocytes to blood vessel walls and their passage through these walls, a process known as diapedesis. CD157 also affects neurogenesis, the process of forming new neurons, and influences the proliferation of neuronal cells.
CD157’s Role in Health and Illness
CD157 plays a role in various physiological processes and has implications in different disease states, making its understanding important for health and disease research.
Immune Regulation and Infection
CD157 influences inflammation and the body’s response to infection. It contributes to macrophage killing of Mycobacterium tuberculosis, the bacteria responsible for tuberculosis. A protective role against M. tuberculosis infection in mice has been attributed to CD157, where it enhances the compartmentalization of TLR2 and PKCzeta, driving reactive oxygen species (ROS) production.
Autoimmune Diseases
CD157’s expression is enhanced in bone marrow stromal cell lines from patients with rheumatoid arthritis. The polyclonal B-cell abnormalities observed in rheumatoid arthritis may be partly due to CD157 overexpression in these stromal cells. The concentration of soluble CD157 has also been found to be significantly increased in the pleural fluid of patients with tuberculous pleurisy compared to those with pneumonia or lung cancer.
Cancer
In the context of cancer, CD157 is highly expressed in acute myeloid leukemia (AML) and is being evaluated as a diagnostic marker, therapeutic target, and a means to monitor treatment progress. CD157-driven intracellular signals in AML cells can protect them from programmed cell death and reduce their sensitivity to chemotherapy. CD157 has also been reported to promote disease progression in epithelial ovarian cancer and malignant pleural mesothelioma.
Tissue Development and Neurodegeneration
CD157 also contributes to tissue development and regeneration, with a role in the self-renewal of stem cells in the intestines and the proliferation of stem and progenitor cells in the lungs. In the nervous system, CD157 has been identified as a risk factor for neurodegeneration, particularly in Parkinson’s disease. Genetic variants of CD157 have been linked to neuropsychiatric diseases, including Parkinson’s disease, autism spectrum disorders, sleep disorders, depressive disorders, and restless leg syndrome.