The Retromer Component SNX6 Interacts With Dynactin p150(Glued) and Mediates endosome-to-TGN Transport

Cell Res. 2009 Dec;19(12):1334-49. doi: 10.1038/cr.2009.130. Epub 2009 Nov 24.

Abstract

The retromer is a protein complex that mediates retrograde transport of transmembrane cargoes from endosomes to the trans-Golgi network (TGN). It is comprised of a cargo-selection subcomplex of Vps26, Vps29 and Vps35 and a membrane-binding coat subcomplex of sorting nexins (SNXs). Previous studies identified SNX1/2 as one of the components of the SNX subcomplex, and SNX5/6 as candidates for the second SNX. How the retromer-associated cargoes are recognized and transported by molecular motors are largely unknown. In this study, we found that one of SNX1/2's dimerization partners, SNX6, interacts with the p150(Glued) subunit of the dynein/dynactin motor complex. We present evidence that SNX6 is a component of the retromer, and that recruitment of the motor complex to the membrane-associated retromer requires the SNX6-p150(Glued) interaction. Disruption of the SNX6-p150(Glued) interaction causes failure in formation and detachment of the tubulovesicular sorting structures from endosomes and results in block of CI-MPR retrieval from endosomes to the TGN. These observations indicate that in addition to SNX1/2, SNX6 in association with the dynein/dynactin complex drives the formation and movement of tubular retrograde intermediates.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Dynactin Complex
  • Dyneins / metabolism
  • Endosomes / genetics
  • Endosomes / metabolism*
  • Endosomes / ultrastructure
  • HeLa Cells
  • Humans
  • Intracellular Membranes / metabolism*
  • Intracellular Membranes / ultrastructure
  • Microtubule-Associated Proteins / genetics*
  • Microtubule-Associated Proteins / metabolism
  • Microtubules / genetics
  • Microtubules / metabolism
  • Microtubules / ultrastructure
  • Protein Transport / physiology
  • Sorting Nexins
  • Vesicular Transport Proteins / genetics
  • Vesicular Transport Proteins / metabolism*
  • trans-Golgi Network / genetics
  • trans-Golgi Network / metabolism*
  • trans-Golgi Network / ultrastructure

Substances

  • DCTN1 protein, human
  • Dynactin Complex
  • Microtubule-Associated Proteins
  • SNX1 protein, human
  • SNX6 protein, human
  • Sorting Nexins
  • Vesicular Transport Proteins
  • Dyneins