11.3 Glycobiology and Cell-Cell Recognition

Carbohydrates play a crucial role in cell-cell interactions, acting as cellular "fingerprints" on cell surfaces. They're involved in recognition processes, adhesion, signaling, and communication, shaping everything from blood types to sperm-egg recognition.

Lectins, proteins that bind specific carbohydrates, are key players in these interactions. They come in various types, each with unique binding preferences, and are involved in processes like cell adhesion, immune responses, and even fertilization.

Carbohydrates in Cell-Cell Interactions

Role of carbohydrates in cell recognition

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• Carbohydrates function as cell surface markers forming unique sugar patterns on glycoproteins and glycolipids embedded in cell membranes act as cellular "fingerprints" (ABO blood types)
• Recognition processes involve specific carbohydrate-protein interactions crucial for cell-cell adhesion, signaling, and communication (sperm-egg recognition)
• Adhesion molecules like selectins bind specific carbohydrates while integrins interact with glycosylated extracellular matrix components facilitating cell attachment and movement
• Immune system utilizes carbohydrate recognition for antigen identification and pathogen binding leading to clearance of foreign substances
• Embryonic development relies on carbohydrate interactions guiding cell migration and tissue formation shaping organ structures

Structure and function of lectins

• Lectins are carbohydrate-binding proteins with high specificity for certain sugar structures enabling precise molecular recognition
• Structural features include carbohydrate recognition domains (CRDs) and multimeric arrangements increasing binding strength and avidity
• Types encompass C-type lectins (calcium-dependent), galectins (β-galactoside-binding), and siglecs (sialic acid-binding) each with distinct binding preferences
• Functions in cell-cell interactions involve mediating cell adhesion, aggregation, signal transduction, and pathogen recognition triggering immune responses
• Lectin-mediated processes include sperm-egg recognition during fertilization, lymphocyte homing to specific tissues, and facilitating bacterial and viral attachment to host cells

Glycocalyx and Glycosylation in Health and Disease

Significance of the glycocalyx

• Glycocalyx forms a carbohydrate-rich layer on cell surfaces composed of glycoproteins, glycolipids, and proteoglycans creating a protective coating
• Cellular communication enhanced through facilitating cell-cell recognition, adhesion, receptor-ligand interactions, and modulating signal transduction pathways
• Immune response regulation involves pathogen recognition, complement activation control, and modulation of leukocyte adhesion and extravasation processes
• Endothelial glycocalyx regulates vascular permeability and mediates mechanotransduction of shear stress influencing blood flow dynamics
• Protection and lubrication provided by acting as a physical barrier against pathogens and reducing cell-cell friction in tissues (synovial fluid)

Aberrant glycosylation in diseases

• Altered glycosylation patterns characterize various diseases including cancer (changes in cell surface glycans), autoimmune disorders (exposure of cryptic epitopes), and congenital disorders of glycosylation (CDG)
• Cancer progression and metastasis associated with increased sialylation and fucosylation altering cell adhesion properties and enabling immune evasion
• Inflammatory diseases exhibit changes in mucin glycosylation (inflammatory bowel disease) and altered glycosylation patterns (rheumatoid arthritis) affecting tissue function
• Infectious diseases exploit host glycans for pathogen binding while glycosylation changes occur in viral infections (influenza virus hemagglutinin)
• Diagnostic and therapeutic implications include developing glycan-based biomarkers for disease detection and targeting aberrant glycosylation for drug development
• Glycoengineering approaches focus on modifying cell surface glycans for therapeutic purposes and creating glycan-based vaccines and immunotherapies