An essential role of Hrs/Vps27 in endosomal cholesterol trafficking

Cell Rep. 2012 Jan 26;1(1):29-35. doi: 10.1016/j.celrep.2011.10.004. Epub 2012 Jan 26.

Abstract

The endosomal sorting complex required for transport (ESCRT) plays a crucial role in the degradation of ubiquitinated endosomal membrane proteins. Here, we report that Hrs, a key protein of the ESCRT-0 complex, is required for the transport of low-density lipoprotein-derived cholesterol from endosomes to the endoplasmic reticulum. This function of Hrs in cholesterol transport is distinct from its previously defined role in lysosomal sorting and downregulation of membrane receptors via the ESCRT pathway. In line with this, knocking down other ESCRT proteins does not cause prominent endosomal cholesterol accumulation. Importantly, the localization and biochemical properties of key cholesterol-sorting proteins, NPC1 and NPC2, appear to be unchanged upon Hrs knockdown. Our data identify Hrs as a regulator of endosomal cholesterol trafficking and provide additional insights into the budding of intralumenal vesicles.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biological Transport
  • Carrier Proteins / metabolism
  • Cell Compartmentation
  • Cholesterol / metabolism*
  • Endoplasmic Reticulum / metabolism
  • Endosomal Sorting Complexes Required for Transport / metabolism*
  • Endosomes / metabolism*
  • Gene Knockdown Techniques
  • Glycoproteins / metabolism
  • HeLa Cells
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Intracellular Space / metabolism
  • Lipoproteins, LDL / metabolism
  • Lysosomes / metabolism
  • Membrane Glycoproteins / metabolism
  • Phosphoproteins / metabolism*
  • Vesicular Transport Proteins

Substances

  • Carrier Proteins
  • Endosomal Sorting Complexes Required for Transport
  • Glycoproteins
  • Intracellular Signaling Peptides and Proteins
  • Lipoproteins, LDL
  • Membrane Glycoproteins
  • NPC1 protein, human
  • NPC2 protein, human
  • Phosphoproteins
  • Vesicular Transport Proteins
  • hepatocyte growth factor-regulated tyrosine kinase substrate
  • Cholesterol