2. Academic Validation
  3. An ER-Associated Pathway Defines Endosomal Architecture for Controlled Cargo Transport

An ER-Associated Pathway Defines Endosomal Architecture for Controlled Cargo Transport

  • Cell. 2016 Jun 30;166(1):152-66. doi: 10.1016/j.cell.2016.05.078.
Marlieke L M Jongsma 1,  Ilana Berlin 2,  Ruud H M Wijdeven 3,  Lennert Janssen 3,  George M C Janssen 4,  Malgorzata A Garstka 3,  Hans Janssen 3,  Mark Mensink 3,  Peter A van Veelen 4,  Robbert M Spaapen 5,  Jacques Neefjes 6
Affiliations

Affiliations

  • 1 Division of Cell Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands; Department of Immunopathology, Sanquin Research and Landsteiner Laboratory AMC/UvA, Plesmanlaan 125, 1066 CX Amsterdam, the Netherlands.
  • 2 Division of Cell Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands. Electronic address: i.berlin@nki.nl.
  • 3 Division of Cell Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands.
  • 4 Department of Immunohematology and Blood Transfusion, Leiden University Medical Centre, P.O. Box 9600, 2300 RC Leiden, the Netherlands.
  • 5 Department of Immunopathology, Sanquin Research and Landsteiner Laboratory AMC/UvA, Plesmanlaan 125, 1066 CX Amsterdam, the Netherlands.
  • 6 Division of Cell Biology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands; Department of Chemical Immunology, Leiden University Medical Centre, P.O. Box 9600, 2300 RC Leiden, the Netherlands. Electronic address: j.neefjes@nki.nl.
PMID: 27368102 DOI: 10.1016/j.cell.2016.05.078
Abstract

Through a network of progressively maturing vesicles, the endosomal system connects the cell's interior with extracellular space. Intriguingly, this network exhibits a bilateral architecture, comprised of a relatively immobile perinuclear vesicle "cloud" and a highly dynamic peripheral contingent. How this spatiotemporal organization is achieved and what function(s) it curates is unclear. Here, we reveal the endoplasmic reticulum (ER)-located ubiquitin Ligase Ring finger protein 26 (RNF26) as the global architect of the entire endosomal system, including the trans-Golgi network (TGN). To specify perinuclear vesicle coordinates, catalytically competent RNF26 recruits and ubiquitinates the scaffold p62/sequestosome 1 (p62/SQSTM1), in turn attracting ubiquitin-binding domains (UBDs) of various vesicle adaptors. Consequently, RNF26 restrains fast transport of diverse vesicles through a common molecular mechanism operating at the ER membrane, until the deubiquitinating Enzyme USP15 opposes RNF26 activity to allow vesicle release into the cell's periphery. By drawing the endosomal system's architecture, RNF26 orchestrates endosomal maturation and trafficking of cargoes, including signaling receptors, in space and time.

Keywords

E3 ligase; EGFR signaling; EPS15; ER; RNF26; TAX1BP1; TGN; TOLLIP; USP15; endosomes; lysosomes; perinuclear; transport; ubiquitin.

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