The Rab11-binding protein RELCH/KIAA1468 controls intracellular cholesterol distribution

J Cell Biol. 2018 May 7;217(5):1777-1796. doi: 10.1083/jcb.201709123. Epub 2018 Mar 7.


Cholesterol, which is endocytosed to the late endosome (LE)/lysosome, is delivered to other organelles through vesicular and nonvesicular transport mechanisms. In this study, we discuss a novel mechanism of cholesterol transport from recycling endosomes (REs) to the trans-Golgi network (TGN) through RELCH/KIAA1468, which is newly identified in this study as a Rab11-GTP- and OSBP-binding protein. After treating cells with 25-hydroxycholesterol to induce OSBP relocation from the cytoplasm to the TGN, REs accumulated around the TGN area, but this accumulation was diminished in RELCH- or OSBP-depleted cells. Cholesterol content in the TGN was decreased in Rab11-, RELCH-, and OSBP-depleted cells and increased in the LE/lysosome. According to in vitro reconstitution experiments, RELCH tethers Rab11-bound RE-like and OSBP-bound TGN-like liposomes and promotes OSBP-dependent cholesterol transfer from RE-like to TGN-like liposomes. These data suggest that RELCH promotes nonvesicular cholesterol transport from REs to the TGN through membrane tethering.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biological Transport
  • Cholesterol / metabolism*
  • Endosomes / metabolism
  • Golgi Apparatus / metabolism
  • Golgi Apparatus / ultrastructure
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Intracellular Membranes / metabolism*
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Lysosomes
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Protein Binding
  • Receptors, Steroid / metabolism
  • rab GTP-Binding Proteins / metabolism*
  • trans-Golgi Network / metabolism
  • trans-Golgi Network / ultrastructure


  • Intracellular Signaling Peptides and Proteins
  • RELCH protein, human
  • Receptors, Steroid
  • Relch protein, mouse
  • oxysterol binding protein
  • Cholesterol
  • rab11 protein
  • rab GTP-Binding Proteins

Associated data

  • RefSeq/NM_173187