title: Initiation of clathrin-mediated endocytosis: all you need is two?
abstract: Clathrin-mediated endocytosis is a major route for the retrieval of plasma-membrane cargoes, and defects of this process can cause catastrophic human dysfunctions. However, the processes governing how a clathrin-coated profile (ccp) is initiated are still murky. Despite an ever-growing cast of molecules proposed as triggers of ccp nucleation and increasingly sophisticated bioimaging techniques examining clathrin-mediated endocytosis, it is yet unknown if ccp formation is governed by a universal mechanism. A recent paper by Cocucci et al. has tracked single-molecule events to identify that stable accumulation of ccps requires the near-simultaneous arrival of two AP2 adaptors bridged by one clathrin triskelion. This commentary examines the role of AP2 in cargo-mediated endocytosis in the light of recent advances in biophotonics, chemical inhibitors and genetics, examines the claims of other molecules to be the initiators of ccp formation and proposes future directions in research into this topic. Editor's suggested further reading in BioEssays: The evolution of dynamin to regulate clathrin-mediated endocytosis Abstract Clathrin-mediated endocytosis: What works for small, also works for big Abstract.
authors: Department of Cell Biology, Yale University School of Medicine, New Haven, CT, USA. laura.swan@yale.edu
authors: Laura E
authors: LE
authors: Swan
mesh_terms: D033962:Adaptor Protein Complex 2 / Q000737:chemistry / Q000378:metabolism*; D033942:Adaptor Proteins, Vesicular Transport / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D002966:Clathrin / Q000737:chemistry / Q000378:metabolism*; D022163:Clathrin-Coated Vesicles / Q000737:chemistry / Q000378:metabolism*; D003034:Coated Pits, Cell-Membrane / Q000737:chemistry / Q000378:metabolism*; D004705:Endocytosis; D050556:Fatty Acid-Binding Proteins; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism; D054730:Protein Interaction Domains and Motifs; D013997:Time Factors; D015027:Zebrafish
chemical_list: D033962:Adaptor Protein Complex 2; D033942:Adaptor Proteins, Vesicular Transport; D002966:Clathrin; C524557:FCHO1 protein, human; C497031:FCHO2 protein, human; D050556:Fatty Acid-Binding Proteins; D008565:Membrane Proteins; D019269:Phosphatidylinositol 4,5-Diphosphate