Cell membrane endocytic uptake pathways

Cell membrane endocytic uptake pathways represent the collective mechanisms through which cells internalize extracellular substances and plasma membrane components. These processes, including clathrin-mediated endocytosis (CME), caveolae-mediated endocytosis, and macropinocytosis, are essential for nutrient acquisition, receptor downregulation, and signal transduction regulation (Nature Reviews Molecular Cell Biology, 2009). In a therapeutic context, these pathways are frequently exploited for the delivery of macromolecular drugs, such as antibody-drug conjugates (ADCs) and siRNA-loaded nanoparticles, which require internalization to reach their intracellular sites of action (Journal of Controlled Release, 2014). Dysfunctions in endocytic trafficking are linked to various pathologies, including cancer, where altered receptor recycling can promote tumor growth, and neurodegenerative diseases characterized by impaired protein clearance (Science, 2013). While specific proteins within these pathways like dynamin or clathrin can be targeted by small molecules like dynasore or chlorpromazine, the pathways themselves serve more as a vehicle for drug entry rather than a single druggable receptor (Pharmacological Reviews, 2010). Pathogens, particularly viruses and certain bacteria, also hijack these pathways to gain entry into host cells, making the modulation of endocytosis a potential strategy for anti-infective therapy (Cell, 2011).

Other names

EndocytosisReceptor-mediated endocytosisClathrin-mediated endocytosisCaveolae-mediated endocytosisMacropinocytosisPhagocytosis

Inhibition of clathrin-coated pit formation, inhibition of dynamin-mediated vesicle fission, disruption of lipid rafts, and inhibition of actin-dependent membrane ruffling.