ER-associated retrograde SNAREs and the Dsl1 complex mediate an alternative, Sey1p-independent homotypic ER fusion pathway

Jason V. Rogers, Conor McMahon, Anastasia Baryshnikova, Frederick M. Hughson, Mark D. Rose

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

The peripheral endoplasmic reticulum (ER) network is dynamically maintained by homotypic (ER-ER) fusion. In Saccharomyces cerevisiae, the dynamin-like GTPase Sey1p can mediate ER-ER fusion, but sey1Δ cells have no growth defect and only slightly perturbed ER structure. Recent work suggested that ER-localized soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) mediate a Sey1p-independent ER-ER fusion pathway. However, an alternative explanation - that the observed phenotypes arose from perturbed vesicle trafficking - could not be ruled out. In this study, we used candidate and synthetic genetic array (SGA) approaches to more fully characterize SNARE-mediated ER-ER fusion. We found that Dsl1 complex mutations in sey1Δ cells cause strong synthetic growth and ER structure defects and delayed ER-ER fusion in vivo, additionally implicating the Dsl1 complex in SNARE-mediated ER-ER fusion. In contrast, cytosolic coat protein I (COPI) vesicle coat muta tions in sey1Δ cells caused no synthetic defects, excluding perturbed retrograde trafficking as a cause for the previously observed synthetic defects. Finally, deleting the reticulons that help maintain ER architecture in cells disrupted for both ER-ER fusion pathways caused almost complete inviability. We conclude that the ER SNAREs and the Dsl1 complex directly mediate Sey1p-independent ER-ER fusion and that, in the absence of both pathways, cell viability depends upon membrane curvature-promoting reticulons.

Original languageEnglish (US)
Pages (from-to)3401-3412
Number of pages12
JournalMolecular biology of the cell
Volume25
Issue number21
DOIs
StatePublished - Nov 1 2014

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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