Cell adhesion molecule

Cell adhesion molecules (CAMs) are a class of cell surface proteins that mediate the binding of cells to other cells or to the extracellular matrix (ECM) through a process known as cell adhesion. These molecules are essential for maintaining tissue structure and function, enabling communication between cells, and supporting critical biological processes such as growth, differentiation, contact inhibition, and apoptosis. CAMs also play a role in mechanotransduction, ensuring the ability of organs to function properly by generating force and movement.

Beyond their structural roles, CAMs are involved in cellular signaling and immune responses. Abnormal expression of CAMs has been implicated in a variety of diseases, including cancer, autoimmune disorders, and neurological diseases.

Structure

Most CAMs are single-pass transmembrane receptors composed of three primary domains:

• Intracellular domain – Interacts with the cytoskeleton and intracellular signaling pathways.
• Transmembrane domain – Anchors the molecule within the plasma membrane.
• Extracellular domain – Facilitates binding with other CAMs or ECM components.

CAMs can engage in two types of binding interactions:

• Homophilic binding – CAMs bind to identical CAMs on adjacent cells.
• Heterophilic binding – CAMs bind to different CAM types on adjacent cells.

Functions

Cell adhesion molecules serve multiple critical functions:

• Tissue integrity and structural organization – CAMs contribute to the maintenance of epithelial, connective, muscle, and nervous tissue.
• Cell signaling – They regulate intracellular pathways affecting cell proliferation, differentiation, and survival.
• Cell migration – CAMs facilitate movement during embryogenesis, wound healing, and immune responses.
• Immune system regulation – CAMs mediate interactions between leukocytes, endothelial cells, and antigen-presenting cells.
• Pathogenesis of diseases – Dysregulation of CAM expression is linked to cancer metastasis, neurodegenerative disorders, and autoimmune diseases.

Families of CAMs

CAMs are classified into several superfamilies based on their structural properties and binding mechanisms:

Immunoglobulin Superfamily Cell Adhesion Molecules (IgCAMs)

• These are calcium-independent adhesion molecules that contain one or more immunoglobulin-like domains.
• They mediate cell-cell adhesion in the nervous system, immune system, and epithelial tissues.
• Examples: NCAM (Neural Cell Adhesion Molecule), ICAM-1 (Intercellular Adhesion Molecule-1), VCAM-1 (Vascular Cell Adhesion Molecule-1).

Cadherins

• Calcium-dependent adhesion molecules that mediate cell-cell adhesion.
• They play a critical role in maintaining tissue integrity, embryonic development, and cell differentiation.
• Examples: E-cadherin, N-cadherin, P-cadherin.

Integrins

• Transmembrane receptors that mediate cell-ECM interactions as well as some cell-cell interactions.
• Integrins consist of α and β subunits that form heterodimers.
• They regulate cell migration, survival, and signaling.
• Examples: α5β1 integrin, αvβ3 integrin.

Selectins

• Calcium-dependent adhesion molecules that mediate cell-cell interactions, particularly in the vascular system and immune response.
• They are primarily expressed on endothelial cells, leukocytes, and platelets.
• Examples: L-selectin, E-selectin, P-selectin.

C-Type Lectin-Like Domain Proteins (CTLDs)

• These CAMs contain C-type lectin domains that mediate cell-cell adhesion.
• They play roles in immune system function and pathogen recognition.
• Examples: Dectin-1, DC-SIGN.

Proteoglycans

• Though not traditionally classified as CAMs, proteoglycans interact with other CAMs and ECM components.
• Examples: Syndecans, Glypicans.

Classification Based on Calcium Dependence

CAMs can also be categorized based on their dependence on calcium ions (Ca²⁺):

• Calcium-independent CAMs: IgCAMs
• Calcium-dependent CAMs: Cadherins, Integrins, Selectins

Clinical Significance

Abnormal expression or dysfunction of CAMs is associated with multiple diseases:

• Cancer – Altered CAM expression can promote tumor progression, angiogenesis, and metastasis.
• Autoimmune diseases – CAM dysregulation contributes to conditions like rheumatoid arthritis, multiple sclerosis, and inflammatory bowel disease.
• Neurological disorders – Defects in CAM function are linked to Alzheimer’s disease, autism spectrum disorders, and schizophrenia.
• Infectious diseases – CAMs facilitate pathogen adhesion in bacterial and viral infections.

Related pages

• Extracellular matrix
• Cell signaling
• Cytoskeleton
• Integrin signaling
• Cancer metastasis
• Tissue engineering

• Cell membrane
• Cell migration
• Immunological synapse
• Trogocytosis

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