Clathrin mediated endocytosis (CME) is the main route of receptor internalization in mammalian cells and this well conserved mechanism has been intensively studied for over 40yrs. In the general or 'canonical' model of CME clathrin coated pits form stochastically at the plasma membrane and coated pit curvature develops as the coated pit grows through clathrin polymerization. However, the canonical model of CME does not explain the diversity of endocytically active clathrin coated structures (CCSs) found at the plasma membrane by both electron and light microscopy. In this review we examine the canonical model of CME, highlight discrepancies with published experimental data and suggest future avenues of exploration while paying particular attention to the relationship between clathrin coated pits, plaques, sites of adhesion and the formation of endocytic 'hotspots'.
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