Clathrinmediated

Clathrin-mediated endocytosis, often abbreviated as CME, is a major cellular pathway for the selective internalization of receptors, nutrients, and other extracellular molecules. In CME, clathrin triskelions assemble into a lattice on the cytosolic side of the plasma membrane, forming clathrin-coated pits that sculpt into vesicles. Adaptor proteins, particularly the AP-2 complex, recognize cargo and link receptors to the assembling coat, helping to recruit clathrin and other accessory factors. As the pit deepens, dynamin, a GTPase, pinches off the neck of the budding vesicle to release a clathrin-coated vesicle into the cytosol.

Following vesicle scission, the clathrin coat is rapidly removed by uncoating enzymes, notably HSC70 and auxilin, yielding an uncoated endosome-ready vesicle. The vesicle traffics to early endosomes where cargo is sorted for recycling back to the plasma membrane or delivery to late endosomes and lysosomes for degradation. Common CME cargo includes transferrin and its receptor, low-density lipoprotein receptors, and many signaling receptors.

CME is tightly regulated by signaling pathways and involves a network of endocytic accessory proteins that coordinate coat assembly, cargo selection, and vesicle scission. While CME is the best-characterized endocytic route, other pathways such as caveolin-mediated endocytosis and macropinocytosis operate in parallel, contributing to nutrient uptake and receptor regulation. Impairments in CME components can contribute to diseases, including hypercholesterolemia and neurodegenerative disorders, underscoring its essential role in cellular homeostasis.