EARP is a multisubunit tethering complex involved in endocytic recycling

Nat Cell Biol. 2015 May;17(5):639-50. doi: 10.1038/ncb3129. Epub 2015 Mar 23.

Abstract

Recycling of endocytic receptors to the cell surface involves passage through a series of membrane-bound compartments by mechanisms that are poorly understood. In particular, it is unknown if endocytic recycling requires the function of multisubunit tethering complexes, as is the case for other intracellular trafficking pathways. Herein we describe a tethering complex named endosome-associated recycling protein (EARP) that is structurally related to the previously described Golgi-associated retrograde protein (GARP) complex. The two complexes share the Ang2, Vps52 and Vps53 subunits, but EARP contains an uncharacterized protein, syndetin, in place of the Vps54 subunit of GARP. This change determines differential localization of EARP to recycling endosomes and GARP to the Golgi complex. EARP interacts with the target SNARE syntaxin 6 and various cognate SNAREs. Depletion of syndetin or syntaxin 6 delays recycling of internalized transferrin to the cell surface. These findings implicate EARP in canonical membrane-fusion events in the process of endocytic recycling.

Publication types

  • Research Support, N.I.H., Intramural
  • Video-Audio Media

MeSH terms

  • Animals
  • Cell Membrane / metabolism
  • Endocytosis*
  • Endosomes / metabolism*
  • Golgi Apparatus / metabolism
  • HeLa Cells
  • Humans
  • Mice
  • Microscopy, Confocal
  • Microscopy, Fluorescence
  • Microscopy, Video
  • Multiprotein Complexes / genetics
  • Multiprotein Complexes / metabolism*
  • Neurons / metabolism*
  • Protein Transport
  • Qa-SNARE Proteins / genetics
  • Qa-SNARE Proteins / metabolism
  • RNA Interference
  • Rats, Sprague-Dawley
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Time Factors
  • Transfection
  • Transferrin / metabolism
  • Vesicular Transport Proteins / genetics
  • Vesicular Transport Proteins / metabolism

Substances

  • Multiprotein Complexes
  • Qa-SNARE Proteins
  • Recombinant Fusion Proteins
  • Transferrin
  • VPS51 protein, human
  • VPS52 protein, human
  • VPS53 protein, human
  • Vesicular Transport Proteins