9.C.17. The Unconventional Endocytosis (UncEndo) Family
Endocytosis mediates the uptake of extracellular proteins, micronutrients and transmembrane cell surface proteins. Many viruses, toxins and bacteria hijack endocytosis to infect cells. The canonical pathway is clathrin-mediated endocytosis (CME) and is active in all eukaryotic cells to support critical house-keeping functions. Unconventional mechanisms of endocytosis internalize specific cargoes and support various cellular functions. These clathrin-independent endocytic (CIE) routes use distinct mechanisms: acute signaling-induced membrane remodeling that drives macropinocytosis, activity-dependent bulk endocytosis (ADBE), massive endocytosis (MEND) and EGFR non-clathrin endocytosis (EGFR-NCE) (Renard and Boucrot 2021). Cargo capture and local membrane deformation by cytosolic proteins is used by fast endophilin-mediated endocytosis (FEME), IL-2Rbeta endocytosis and ultrafast endocytosis at synapses. Finally, the formation of endocytic pits by clustering of extracellular lipids or cargoes according to the Glycolipid-Lectin (GL-Lect) hypothesis mediates the uptake of SV40 virus, Shiga and cholera toxins, and galectin-clustered receptors by the CLIC/GEEC and the endophilin-A3-mediated CIE (Renard and Boucrot 2021).