Endocytosis
The cellular process of engulfing extracellular material by folding the cell membrane inward to form vesicles. Receptor-mediated endocytosis is how many peptide-receptor complexes are internalised after binding. Understanding endocytosis is important for peptide drug delivery and receptor dynamics.
Technical Context
Endocytic pathways: clathrin-mediated endocytosis (CME — the primary pathway for receptor internalisation; clathrin triskelia polymerise into coated pits, with cargo selection by adaptor proteins), caveolae-mediated (flask-shaped membrane invaginations enriched in cholesterol and caveolin — involved in some receptor signalling and transcytosis), macropinocytosis (non-specific uptake of large fluid volumes through membrane ruffling — mechanism for some cell-penetrating peptide entry), phagocytosis (specific to professional phagocytes — receptor-mediated ingestion of large particles), and clathrin/caveolae-independent pathways (various mechanisms including flotillin-dependent and GRAF1-dependent). For peptide therapeutics, endocytosis is relevant to: receptor internalisation and signalling (some GPCRs continue to signal from endosomes — endosomal signalling), drug delivery (CPPs and targeted peptide conjugates rely on endocytic uptake), and escape from endosomes (therapeutic cargo must escape into the cytoplasm before lysosomal degradation — the endosomal escape problem).