FERARI is required for Rab11-dependent endocytic recycling

Nat Cell Biol. 2020 Feb;22(2):213-224. doi: 10.1038/s41556-019-0456-5. Epub 2020 Jan 27.

Abstract

Endosomal transport is essential for cellular organization and compartmentalization and cell-cell communication. Sorting endosomes provide a crossroads for various trafficking pathways and determine recycling, secretion or degradation of proteins. The organization of these processes requires membrane-tethering factors to coordinate Rab GTPase function with membrane fusion. Here, we report a conserved tethering platform that acts in the Rab11 recycling pathways at sorting endosomes, which we name factors for endosome recycling and Rab interactions (FERARI). The Rab-binding module of FERARI consists of Rab11FIP5 and rabenosyn-5/RABS-5, while the SNARE-interacting module comprises VPS45 and VIPAS39. Unexpectedly, the membrane fission protein EHD1 is also a FERARI component. Thus, FERARI appears to combine fusion activity through the SM protein VPS45 with pinching activity through EHD1 on SNX-1-positive endosomal membranes. We propose that coordination of fusion and pinching through a kiss-and-run mechanism drives cargo at endosomes into recycling pathways.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Adaptor Proteins, Signal Transducing / metabolism
  • Animals
  • Animals, Genetically Modified
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism
  • Cell Communication
  • Endocytosis / genetics*
  • Endosomes / metabolism*
  • Gene Expression Regulation
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Intestines / cytology
  • Molecular Imaging
  • Oocytes / cytology
  • Oocytes / metabolism
  • Protein Transport
  • Sorting Nexins / genetics
  • Sorting Nexins / metabolism
  • Vesicular Transport Proteins / genetics*
  • Vesicular Transport Proteins / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • Caenorhabditis elegans Proteins
  • EHD1 protein, human
  • RAB11FIP5 protein, human
  • RBSN protein, human
  • RME-1 protein, C elegans
  • SNX-1 protein, C elegans
  • Sorting Nexins
  • VIPAS39 protein, human
  • VPS45 protein, human
  • Vesicular Transport Proteins