CD151 - CD151 molecule |Elisa - Clia - Antibody - Protein

Background

CD151 is a cell-surface protein belonging to the tetraspanin family, a group of transmembrane proteins involved in cell signaling, adhesion, and migration. This protein, encoded by the CD151 gene, is expressed on a wide range of cell types, including epithelial cells, endothelial cells, platelets, and certain hematopoietic cells. CD151 is known to interact with various integrins—primarily integrins α3β1, α6β1, and α6β4—which are crucial for cellular adhesion to the extracellular matrix (ECM) and in forming stable cellular junctions. CD151 is a key player in numerous physiological processes, including wound healing, angiogenesis, hemostasis, and immune responses. Additionally, this protein has been implicated in various diseases, notably cancer metastasis, kidney disease, and platelet-related disorders. Given its integral role in cellular adhesion and signaling, CD151 is considered a therapeutic target in certain diseases.

Protein Structure

CD151 is a type of tetraspanin, featuring a four-pass transmembrane structure with the following key structural domains:

Extracellular Domains:

• CD151 contains two extracellular loops: a small extracellular loop (SEL) and a large extracellular loop (LEL).
• The LEL is the main binding site for integrin interaction and contains regions critical for integrin specificity and affinity. This loop typically includes several conserved cysteine residues, which form disulfide bonds and maintain structural stability.
• The SEL has a less prominent role in protein interaction but may contribute to structural integrity and proper positioning of the LEL.

Transmembrane Domains (TMD):

• CD151 has four α-helical transmembrane domains that anchor it firmly to the plasma membrane and allow it to interact with other transmembrane proteins.
• The TMDs are highly conserved among tetraspanins, providing a stable framework that supports protein-protein interactions with other tetraspanins and integrins within the membrane.

Intracellular Domains:

• The protein also has short N- and C-terminal intracellular regions, which are relatively conserved across tetraspanins and are involved in intracellular signaling.
• The intracellular C-terminal tail contains regions essential for interacting with cytoskeletal and signaling proteins. Although short, these regions play roles in post-translational modifications, particularly palmitoylation, which regulates protein stability and association with lipid rafts.

CD151’s structural domains enable it to function as a "molecular facilitator," assembling specific multi-protein complexes and promoting cell-cell and cell-matrix interactions.

Classification and Subtypes

CD151 is a member of the tetraspanin family of transmembrane proteins, also known as the transmembrane 4 superfamily. Tetraspanins are generally defined by their four transmembrane domains, two extracellular loops, and two short cytoplasmic tails. While CD151 itself does not have subtypes, it shares close structural and functional relationships with other tetraspanins, such as CD9, CD81, and CD63, which also play roles in cell adhesion and migration. CD151 is most closely associated with integrin interactions, particularly integrins α3β1, α6β1, and α6β4, which distinguishes it functionally from other tetraspanins.

Function and Biological Significance

Cell Adhesion and Migration:

• CD151 plays a fundamental role in cell adhesion by forming complexes with integrins, primarily those associated with laminin-binding integrins, such as α3β1, α6β1, and α6β4. These interactions promote stable cell-ECM adhesion, contributing to cellular migration and tissue organization.
• Through its interactions with integrins, CD151 enhances cell migration, particularly in wound healing, where it promotes epithelial cell migration to cover wounded areas. It is also involved in endothelial cell migration, essential for angiogenesis during tissue repair and development.

Signal Transduction:

• CD151 influences various intracellular signaling pathways that affect cell proliferation, differentiation, and survival. Its interactions with integrins activate downstream signaling cascades, including focal adhesion kinase (FAK) and PI3K/Akt pathways.
• The protein can form complexes with other tetraspanins, establishing a network known as the tetraspanin-enriched microdomain (TEM). TEMs serve as hubs for receptor signaling and provide a scaffold for recruiting other signaling proteins.

Angiogenesis:

• CD151 is important in vascular biology, where it supports endothelial cell function and promotes angiogenesis by facilitating interactions with integrin α6β1. It regulates the assembly of endothelial cells during blood vessel formation, a process essential for embryonic development, wound healing, and tumor growth.

Immune Modulation:

• While primarily studied for its role in adhesion and migration, CD151 also contributes to immune function. It is expressed on certain immune cells, where it is involved in immune cell migration and extravasation, aiding cells to reach sites of inflammation or infection.

Platelet Aggregation and Hemostasis:

• CD151 is expressed on platelets and is involved in platelet adhesion to the ECM, especially under conditions of vascular injury. Its interactions with integrins on platelets help to stabilize blood clots, thus contributing to hemostasis.

Clinical Issues

Cancer:

• CD151 is highly expressed in various cancers, including breast, prostate, and lung cancers. Its role in promoting cellular adhesion and migration makes it a key player in cancer metastasis.
• Overexpression of CD151 has been associated with increased invasiveness and poor prognosis in cancers due to its ability to stabilize integrin interactions, promoting tumor cell migration and spread. Research on targeting CD151 for anti-metastatic therapy is ongoing, aiming to block its interactions with integrins to reduce cancer cell adhesion and spread.

Kidney Disease:

• Mutations in CD151 have been linked to kidney disorders, particularly hereditary nephropathy. This condition is characterized by glomerular basement membrane defects, resulting from impaired interactions between CD151 and integrins in kidney cells. Patients with CD151-related nephropathy often experience proteinuria and progressive renal failure.

Hemostatic Disorders:

• Given CD151's role in platelet function, abnormalities in its expression or function may contribute to hemostatic disorders. In some patients, CD151 deficiencies or dysfunctions may result in impaired platelet aggregation, affecting normal blood clotting.

Autoimmune and Inflammatory Diseases:

• CD151 is implicated in inflammatory diseases due to its role in immune cell migration. Its expression on immune cells, particularly those involved in inflammation, suggests that dysregulation could contribute to autoimmune conditions, although the exact mechanisms remain under investigation.

Therapeutic Target:

• CD151’s specific role in cell adhesion and migration makes it a potential therapeutic target for treating cancer, fibrosis, and other diseases involving abnormal cell migration. Efforts to develop CD151-targeted therapies include monoclonal antibodies and small molecule inhibitors that could disrupt its interactions with integrins.

Summary

CD151 is a tetraspanin family protein that plays crucial roles in cellular adhesion, migration, and signaling, particularly through interactions with integrins α3β1, α6β1, and α6β4. Its four-pass transmembrane structure with two extracellular loops enables it to function as a scaffold in cell membranes, facilitating the formation of tetraspanin-enriched microdomains. These structural features support its role in diverse biological processes, including angiogenesis, wound healing, immune responses, and platelet aggregation. CD151’s involvement in cancer metastasis, kidney disease, and platelet function disorders underscores its clinical significance, and it is currently under investigation as a therapeutic target for these conditions. Targeting CD151 or its integrin interactions may offer novel therapeutic strategies for diseases characterized by abnormal cell adhesion and migration.