nonclathrin

Nonclathrin refers to endocytic pathways and vesicles that internalize material at the plasma membrane without forming clathrin-coated pits. These clathrin-independent routes operate alongside clathrin-mediated endocytosis and contribute to receptor turnover, nutrient uptake, and signaling regulation.

Caveolin-mediated endocytosis, via caveolae, uses caveolin proteins and cholesterol-rich lipid microdomains; it is often dynamin-dependent and transports specific lipids and proteins. The clathrin-independent carriers (CLIC)/GEEC pathway internalizes certain glycosylphosphatidylinositol-anchored proteins and fluid-phase cargo, is regulated by Cdc42 and actin, and forms tubular or vesicular carriers. Flotillin-dependent endocytosis uses flotillins and lipid rafts to internalize selected receptors. Macropinocytosis, driven by actin remodeling, engulfs extracellular fluid nonselectively and is largely clathrin-independent. Arf6-dependent endocytosis, controlled by the small GTPase Arf6, also contributes to internalization of particular membrane proteins.

Cargoes and consequences: caveolae handle cholesterol-rich membrane components and certain toxins or pathogens; GEEC/CLIC routes internalize GPI-anchored proteins and receptors not efficiently trafficked by CME; nonclathrin pathways influence signaling by controlling receptor distribution at the plasma membrane.

Clinical and research relevance: understanding nonclathrin pathways clarifies mechanisms of viral entry, cancer cell behavior, and drug delivery; due to pathway overlap and context-dependent participation, the boundaries between clathrin-dependent and -independent endocytosis remain under study.