RINT-1 regulates the localization and entry of ZW10 to the syntaxin 18 complex

Mol Biol Cell. 2006 Jun;17(6):2780-8. doi: 10.1091/mbc.e05-10-0973. Epub 2006 Mar 29.

Abstract

RINT-1 was first identified as a Rad50-interacting protein that participates in radiation-induced G2/M checkpoint control. We have recently reported that RINT-1, together with the dynamitin-interacting protein ZW10 and others, is associated with syntaxin 18, an endoplasmic reticulum (ER)-localized SNARE involved in membrane trafficking between the ER and Golgi. To address the role of RINT-1 in membrane trafficking, we examined the effects of overexpression and knockdown of RINT-1 on Golgi morphology and protein transport from the ER. Overexpression of the N-terminal region of RINT-1, which is responsible for the interaction with ZW10, caused redistribution of ZW10. Concomitantly, ER-to-Golgi transport was blocked and the Golgi was dispersed. Knockdown of RINT-1 also disrupted membrane trafficking between the ER and Golgi. Notably, silencing of RINT-1 resulted in a reduction in the amount of ZW10 associated with syntaxin 18, concomitant with ZW10 redistribution. In contrast, no redistribution or release of RINT-1 from the syntaxin 18 complex was observed when ZW10 expression was reduced. These results taken together suggest that RINT-1 coordinates the localization and function of ZW10 by serving as a link between ZW10 and the SNARE complex comprising syntaxin 18.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brefeldin A / pharmacology
  • Cell Cycle
  • Cell Cycle Proteins / metabolism*
  • Cell Membrane / metabolism
  • Endoplasmic Reticulum / metabolism
  • Golgi Apparatus / metabolism
  • HeLa Cells
  • Humans
  • Intracellular Signaling Peptides and Proteins / deficiency
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Nuclear Proteins / deficiency
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Protein Binding
  • Protein Transport
  • Qa-SNARE Proteins / metabolism*
  • RNA Interference
  • Recombinant Fusion Proteins / metabolism
  • SNARE Proteins / metabolism*
  • Transfection
  • Zinc Fingers

Substances

  • Cell Cycle Proteins
  • Intracellular Signaling Peptides and Proteins
  • Nuclear Proteins
  • Qa-SNARE Proteins
  • RINT1 protein, human
  • Recombinant Fusion Proteins
  • SNARE Proteins
  • ZWINT protein, human
  • Brefeldin A