title: Ligands for clathrin-mediated endocytosis are differentially sorted into distinct populations of early endosomes.
abstract: Cells rely on the correct sorting of endocytic ligands and receptors for proper function. Early endosomes have been considered as the initial sorting station where cargos for degradation separate from those for recycling. Using live-cell imaging to monitor individual endosomes and ligand particles in real time, we have discovered a sorting mechanism that takes place prior to early endosome entry. We show that early endosomes are in fact comprised of two distinct populations: a dynamic population that is highly mobile on microtubules and matures rapidly toward late endosomes and a static population that matures much more slowly. Several cargos destined for degradation are preferentially targeted to the dynamic endosomes, whereas the recycling ligand transferrin is nonselectively delivered to all early endosomes and effectively enriched in the larger, static population. This pre-early endosome sorting process begins at clathrin-coated vesicles, depends on microtubule-dependent motility, and appears to involve endocytic adaptors.
authors.affiliation: Howard Hughes Medical Institute, Harvard University, Cambridge, MA 02138, USA.
authors.forename: Melike
authors.initials: M
authors.lastname: Lakadamyali
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Rust
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Zhuang
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002966:Clathrin / Q000378:metabolism*; D022163:Clathrin-Coated Vesicles / Q000737:chemistry / Q000378:metabolism*; D011992:Endosomes / Q000737:chemistry / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000378:metabolism; D005456:Fluorescent Dyes / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D008024:Ligands; D008077:Lipoproteins, LDL / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism; D009975:Orthomyxoviridae / Q000378:metabolism; D021381:Protein Transport / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014168:Transferrin / Q000378:metabolism; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D020696:rab5 GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D000090802:rab7 GTP-Binding Proteins
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D002966:Clathrin; D005456:Fluorescent Dyes; D008024:Ligands; D008077:Lipoproteins, LDL; D011993:Recombinant Fusion Proteins; D014168:Transferrin; D000090802:rab7 GTP-Binding Proteins; D004815:Epidermal Growth Factor; D020691:rab GTP-Binding Proteins; D020696:rab5 GTP-Binding Proteins