Silencing of mammalian Sar1 isoforms reveals COPII-independent protein sorting and transport

Traffic. 2013 Jun;14(6):691-708. doi: 10.1111/tra.12060. Epub 2013 Mar 15.

Abstract

The Sar1 GTPase coordinates the assembly of coat protein complex-II (COPII) at specific sites of the endoplasmic reticulum (ER). COPII is required for ER-to-Golgi transport, as it provides a structural and functional framework to ship out protein cargoes produced in the ER. To investigate the requirement of COPII-mediated transport in mammalian cells, we used small interfering RNA (siRNA)-mediated depletion of Sar1A and Sar1B. We report that depletion of these two mammalian forms of Sar1 disrupts COPII assembly and the cells fail to organize transitional elements that coordinate classical ER-to-Golgi protein transfer. Under these conditions, minimal Golgi stacks are seen in proximity to juxtanuclear ER membranes that contain elements of the intermediate compartment, and from which these stacks coordinate biosynthetic transport of protein cargo, such as the vesicular stomatitis virus G protein and albumin. Here, transport of procollagen-I is inhibited. These data provide proof-of-principle for the contribution of alternative mechanisms that support biosynthetic trafficking in mammalian cells, providing evidence of a functional boundary associated with a bypass of COPII.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • COP-Coated Vesicles / metabolism*
  • Endoplasmic Reticulum / metabolism
  • Gene Silencing
  • Golgi Apparatus / metabolism
  • HeLa Cells
  • Hep G2 Cells
  • Humans
  • Monomeric GTP-Binding Proteins / genetics
  • Monomeric GTP-Binding Proteins / metabolism*
  • Procollagen / metabolism
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Protein Transport
  • RNA, Small Interfering / genetics
  • Secretory Pathway / genetics*

Substances

  • Procollagen
  • Protein Isoforms
  • RNA, Small Interfering
  • SAR1A protein, human
  • Monomeric GTP-Binding Proteins

Grants and funding