The TRAPP complex mediates secretion arrest induced by stress granule assembly

EMBO J. 2019 Oct 1;38(19):e101704. doi: 10.15252/embj.2019101704. Epub 2019 Aug 20.

Abstract

The TRAnsport Protein Particle (TRAPP) complex controls multiple membrane trafficking steps and is strategically positioned to mediate cell adaptation to diverse environmental conditions, including acute stress. We have identified the TRAPP complex as a component of a branch of the integrated stress response that impinges on the early secretory pathway. The TRAPP complex associates with and drives the recruitment of the COPII coat to stress granules (SGs) leading to vesiculation of the Golgi complex and arrest of ER export. The relocation of the TRAPP complex and COPII to SGs only occurs in cycling cells and is CDK1/2-dependent, being driven by the interaction of TRAPP with hnRNPK, a CDK substrate that associates with SGs when phosphorylated. In addition, CDK1/2 inhibition impairs TRAPP complex/COPII relocation to SGs while stabilizing them at ER exit sites. Importantly, the TRAPP complex controls the maturation of SGs. SGs that assemble in TRAPP-depleted cells are smaller and are no longer able to recruit RACK1 and Raptor, two TRAPP-interactive signaling proteins, sensitizing cells to stress-induced apoptosis.

Keywords: COPII; Cdk; TRAPP complex; integrated stress response; stress granules.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CDC2 Protein Kinase / metabolism
  • COP-Coated Vesicles / metabolism*
  • Cell Line
  • Cyclin-Dependent Kinase 2 / metabolism
  • Endoplasmic Reticulum / metabolism
  • HeLa Cells
  • Humans
  • Membrane Transport Proteins / metabolism*
  • Rats
  • Stress, Physiological*

Substances

  • Membrane Transport Proteins
  • CDC2 Protein Kinase
  • Cyclin-Dependent Kinase 2