ClathrinBinding

Clathrin-binding refers to the molecular interactions between clathrin and its binding partners, a critical process in cellular trafficking and endocytosis. Clathrin is a protein that assembles into polyhedral cages known as clathrin-coated pits and vesicles, facilitating the transport of cargo across the cell membrane. These interactions are mediated through specific binding domains on clathrin or associated adaptor proteins, such as AP-2 (adaptor protein complex 2), which link clathrin to membrane-bound receptors and cargo molecules.

The primary clathrin-binding motifs include the NPXY and YXX sequences found in transmembrane proteins, which are recognized by the μ2 subunit of AP-2. Additionally, clathrin itself contains a clathrin-binding domain (CBD) that interacts with proteins like dynamin, auxilin, and the Hsc70 heat shock protein, which are involved in vesicle uncoating and membrane fission. These interactions are essential for the formation, scission, and recycling of clathrin-coated vesicles, ensuring proper sorting and delivery of extracellular and intracellular cargo.

Disruptions in clathrin-binding can lead to defects in endocytosis, exocytosis, and intracellular trafficking, contributing to various cellular dysfunctions and diseases. For example, mutations affecting clathrin or adaptor proteins have been linked to neurological disorders, immune deficiencies, and metabolic disorders. Research into clathrin-binding mechanisms continues to provide insights into cellular homeostasis and potential therapeutic targets for diseases involving trafficking impairments.