title: APPL endosomes are not obligatory endocytic intermediates but act as stable cargo-sorting compartments.
abstract: Endocytosis allows cargo to enter a series of specialized endosomal compartments, beginning with early endosomes harboring Rab5 and its effector EEA1. There are, however, additional structures labeled by the Rab5 effector APPL1 whose role in endocytic transport remains unclear. It has been proposed that APPL1 vesicles are transport intermediates that convert into EEA1 endosomes. Here, we tested this model by analyzing the ultrastructural morphology, kinetics of cargo transport, and stability of the APPL1 compartment over time. We found that APPL1 resides on a tubulo-vesicular compartment that is capable of sorting cargo for recycling or degradation and that displays long lifetimes, all features typical of early endosomes. Fitting mathematical models to experimental data rules out maturation of APPL1 vesicles into EEA1 endosomes as a primary mechanism for cargo transport. Our data suggest instead that APPL1 endosomes represent a distinct population of Rab5-positive sorting endosomes, thus providing important insights into the compartmental organization of the early endocytic pathway.
authors.affiliation: Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany.
authors.forename: Inna
authors.initials: I
authors.lastname: Kalaidzidis
authors.affiliation: Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany International Institute of Molecular and Cell Biology, 02-109 Warsaw, Poland.
authors.forename: Marta
authors.initials: M
authors.lastname: Miaczynska
authors.affiliation: International Institute of Molecular and Cell Biology, 02-109 Warsaw, Poland Nencki Institute of Experimental Biology, 02-093 Warsaw, Poland.
authors.forename: Marta
authors.initials: M
authors.lastname: Brewińska-Olchowik
authors.affiliation: International Institute of Molecular and Cell Biology, 02-109 Warsaw, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Hupalowska
authors.affiliation: Institute for Molecular Bioscience and Centre for Microscopy and Microanalysis, University of Queensland St. Lucia, Brisbane, Australia 4072.
authors.forename: Charles
authors.initials: C
authors.lastname: Ferguson
authors.affiliation: Institute for Molecular Bioscience and Centre for Microscopy and Microanalysis, University of Queensland St. Lucia, Brisbane, Australia 4072.
authors.forename: Robert G
authors.initials: RG
authors.lastname: Parton
authors.affiliation: Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, 119991 Moscow, Russia.
authors.forename: Yannis
authors.initials: Y
authors.lastname: Kalaidzidis
authors.affiliation: Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany zerial@MPI-CBG.de.
authors.forename: Marino
authors.initials: M
authors.lastname: Zerial
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000502:physiology*; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D021381:Protein Transport
chemical_list: C464801:APPL1 protein, human; D048868:Adaptor Proteins, Signal Transducing