Nuclear envelope-associated endosomes deliver surface proteins to the nucleus

Nat Commun. 2015 Sep 10:6:8218. doi: 10.1038/ncomms9218.

Abstract

Endocytosis directs molecular cargo along three main routes: recycling to the cell surface, transport to the Golgi apparatus or degradation in endolysosomes. Pseudomonas exotoxin A (PE) is a bacterial protein that typically traffics to the Golgi and then the endoplasmic reticulum before translocating to the cytosol. Here we show that a substantial fraction of internalized PE is also located in nuclear envelope-associated endosomes (NAE), which display limited mobility, exhibit a propensity to undergo fusion and readily discharge their contents into the nuclear envelope. Electron microscopy and protein trapping in the nucleus indicate that NAE mediate PE transfer into the nucleoplasm. RNAi screening further revealed that NAE-mediated transfer depends on the nuclear envelope proteins SUN1 and SUN2, as well as the Sec61 translocon complex. These data reveal a novel endosomal route from the cell surface to the nucleoplasm that facilitates the accumulation of extracellular and cell surface proteins in the nucleus.

MeSH terms

  • ADP Ribose Transferases / metabolism*
  • Bacterial Toxins / metabolism*
  • Cell Line, Tumor
  • Cell Nucleus / metabolism*
  • Cytosol / metabolism
  • Endocytosis*
  • Endoplasmic Reticulum / metabolism
  • Endosomes / metabolism*
  • Exotoxins / metabolism*
  • Fluorescent Antibody Technique
  • Gene Knockdown Techniques
  • Golgi Apparatus / metabolism
  • HeLa Cells
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism
  • Microscopy, Confocal
  • Microscopy, Electron
  • Microtubule-Associated Proteins / genetics*
  • Microtubule-Associated Proteins / metabolism
  • Nuclear Envelope / metabolism*
  • Nuclear Localization Signals
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / metabolism
  • Protein Transport
  • Pseudomonas aeruginosa Exotoxin A
  • SEC Translocation Channels
  • Virulence Factors / metabolism*

Substances

  • Bacterial Toxins
  • Exotoxins
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Microtubule-Associated Proteins
  • Nuclear Localization Signals
  • Nuclear Proteins
  • SEC Translocation Channels
  • SUN1 protein, human
  • SUN2 protein, human
  • Virulence Factors
  • ADP Ribose Transferases