CD82 - CD82 molecule |Elisa - Clia - Antibody - Protein

Background

CD82, also known as KAI1 (Kangai 1), is a member of the tetraspanin family, a group of integral membrane proteins involved in the regulation of cell development, motility, adhesion, and immune responses. CD82 is of particular interest in cancer biology due to its role as a metastasis suppressor gene. It was initially identified as a tumor suppressor in prostate cancer, and subsequent studies have demonstrated that it plays a significant role in suppressing metastasis across a range of cancers.

The CD82 gene is located on chromosome 11p11.2 and is ubiquitously expressed in various cell types, including epithelial cells, immune cells, and neurons. The primary function of CD82 is to regulate cell-cell interactions and modulate signal transduction pathways. Importantly, CD82 is involved in the regulation of immune cell activation, adhesion, and migration, making it a vital component in both immune responses and cancer progression.

Protein Structure

CD82 is a tetraspanin protein that spans the plasma membrane four times, a characteristic feature of the tetraspanin family. Its structure consists of four transmembrane helices, two extracellular loops, and short cytoplasmic domains at both the N- and C-termini.

Transmembrane Domains:

• CD82 is anchored in the membrane via four α-helical transmembrane domains. These domains are crucial for the protein's stability and interaction with the lipid bilayer.
• The transmembrane regions are involved in forming tetraspanin-enriched microdomains (TEMs), where they interact with other tetraspanins and transmembrane proteins. These domains also contribute to the localization of CD82 in membrane rafts, specialized regions of the plasma membrane enriched with cholesterol and sphingolipids.

Extracellular Loops:

• CD82 has two extracellular loops: a small loop (EC1) and a larger loop (EC2). The EC2 loop is critical for its interactions with other proteins, such as integrins and growth factor receptors. It contains conserved cysteine residues that form disulfide bonds, stabilizing the structure of the protein.
• The EC2 loop of CD82 plays an essential role in mediating its anti-metastatic effects by regulating cell adhesion and migration. Additionally, it is involved in forming interactions with other tetraspanins, helping to organize functional multiprotein complexes at the cell membrane.

Cytoplasmic Domains:

• CD82 contains short cytoplasmic N- and C-terminal domains that are involved in the intracellular signaling and trafficking of the protein. These regions allow CD82 to interact with proteins of the cytoskeleton, facilitating its role in cell migration and adhesion.
• The cytoplasmic tails may also regulate the association of CD82 with intracellular signaling pathways, impacting processes such as cell proliferation, differentiation, and immune responses.

Classification and Subtypes

CD82 is a part of the tetraspanin family, which includes over 30 proteins that share a similar structural topology, characterized by their four transmembrane domains. These proteins are classified based on their ability to organize tetraspanin-enriched microdomains (TEMs), which serve as scaffolding platforms for a variety of cell surface receptors, integrins, and signaling molecules.

CD82 itself does not have distinct subtypes but interacts with multiple partners to form distinct functional complexes in different cellular contexts. For example, CD82 interacts with integrins to regulate cell adhesion, and with EGFR (epidermal growth factor receptor) to modulate growth factor signaling.

Function and Biological Significance

CD82 plays a wide range of roles in biological processes, particularly in cancer suppression, immune cell regulation, and cell adhesion.

Metastasis Suppression:

• CD82 is a well-characterized tumor metastasis suppressor. It inhibits the spread of cancer cells by regulating key processes like cell adhesion, migration, and invasion. CD82 reduces the ability of tumor cells to detach from the primary site and invade surrounding tissues, limiting the metastatic potential of cancers such as prostate, breast, lung, and colon cancers.
• Mechanistically, CD82 influences the activity of integrins and matrix metalloproteinases (MMPs), which are involved in cell migration and tissue remodeling. By modulating these pathways, CD82 suppresses the movement of cancer cells through the extracellular matrix, thus limiting metastasis.

Tetraspanin-Enriched Microdomains (TEMs):

• CD82 is a key organizer of tetraspanin-enriched microdomains. These microdomains facilitate the clustering and assembly of transmembrane receptors, integrins, and signaling molecules into functional complexes. Through its role in TEMs, CD82 regulates cell signaling, adhesion, and migration.
• CD82 interacts with integrins such as α4β1 and α5β1, modulating the way cells interact with the extracellular matrix and influencing immune responses and wound healing.

Immune Regulation:

• CD82 is involved in immune cell regulation, particularly in T and B cells. It contributes to the regulation of T cell activation and proliferation, potentially by forming complexes with other tetraspanins and CD4 or CD8 molecules on the surface of T cells.
• In B cells, CD82 is involved in antigen presentation and the formation of immune synapses, facilitating effective immune responses. It may also play a role in the maturation of dendritic cells, which are crucial for antigen presentation and the activation of T cells.

Cell Adhesion and Migration:

• CD82 modulates cell adhesion and migration by regulating the activity of integrins and cytoskeletal elements. By influencing the dynamics of focal adhesions and actin remodeling, CD82 can control how cells adhere to and move across the extracellular matrix.
• This function is particularly important in the context of cancer, where altered cell adhesion and increased motility are hallmarks of metastatic disease. By maintaining proper cell adhesion, CD82 suppresses the detachment and migration of cancer cells, contributing to its anti-metastatic properties.

Role in Viral Infections:

• CD82 has also been implicated in the regulation of viral infections, particularly in HIV and hepatitis C virus (HCV). It has been suggested that CD82 can inhibit HIV-1 infection by interfering with the virus's entry into host cells. The exact mechanisms are still under investigation, but CD82's role in organizing membrane microdomains may influence how viruses interact with host cell receptors.

Clinical Issues

The loss or downregulation of CD82 expression has been linked to the progression of various cancers, underscoring its role as a tumor suppressor.

Cancer Metastasis:

• CD82 is widely recognized for its ability to suppress cancer metastasis. The expression of CD82 is often reduced or lost in advanced stages of several cancers, including prostate, breast, lung, colorectal, and pancreatic cancers. The loss of CD82 function is associated with increased tumor cell migration, invasion, and metastasis.
• Restoring CD82 expression in cancer cells has been shown to reduce their metastatic potential, making CD82 a potential therapeutic target for inhibiting cancer spread. Researchers are investigating ways to enhance CD82 expression or mimic its functions as a strategy to block cancer metastasis.

Immune Dysregulation:

• CD82 plays a role in regulating immune cell activation and adhesion, and alterations in its expression or function could contribute to immune disorders. Dysregulation of CD82 in immune cells might affect the proper formation of immune synapses or the activation of T cells, potentially leading to altered immune responses in diseases like autoimmune disorders.

Viral Infections:

• CD82 has shown potential as a target for controlling viral infections, particularly in the context of HIV and hepatitis C virus (HCV). By disrupting the interactions between viruses and host cell receptors, CD82 may provide a novel approach to prevent viral entry and reduce viral replication.

Summary

CD82 is a member of the tetraspanin family, with critical roles in regulating cell adhesion, migration, and immune responses. Structurally, CD82 is a four-pass transmembrane protein with two extracellular loops that facilitate interactions with other cell surface proteins and integrins. Functionally, CD82 acts as a tumor metastasis suppressor by regulating the activity of integrins and the extracellular matrix, thereby inhibiting cancer cell migration and invasion.

In the immune system, CD82 regulates T cell activation and antigen presentation by organizing tetraspanin-enriched microdomains on the cell surface. Clinically, the loss of CD82 expression is associated with metastatic cancer progression, making it an important biomarker and therapeutic target for anti-metastatic therapies. CD82 may also play a role in viral infections, offering potential avenues for antiviral strategies.

Overall, CD82 is a multifaceted protein with significant implications in cancer biology, immune regulation, and viral infections, and it holds promise as a therapeutic target in these contexts.