A sphingolipid-dependent diffusion barrier confines ER stress to the yeast mother cell.
In many cell types, lateral diffusion barriers compartmentalize the plasma membrane and, at least in budding yeast, the endoplasmic reticulum (ER). However, the molecular nature of these barriers, their mode of action and their cellular functions are unclear. Here, we show that misfolded proteins of the ER remain confined into the mother compartment of budding yeast cells. Confinement required the formation of a lateral diffusion barrier in the form of a distinct domain of the ER-membrane at the bud neck, in a septin-, Bud1 GTPase- and sphingolipid-dependent manner. The sphingolipids, but not Bud1, also contributed to barrier formation in the outer membrane of the dividing nucleus. Barrier-dependent confinement of ER stress into the mother cell promoted aging. Together, our data clarify the physical nature of lateral diffusion barriers in the ER and establish the role of such barriers in the asymmetric segregation of proteotoxic misfolded proteins during cell division and aging.DOI: http://dx.doi.org/10.7554/eLife.01883.001.
Institute of Biochemistry, Department of Biology, ETH Zürich, Zürich, Switzerland.
Lori
L
Clay
Institute of Biochemistry, Department of Biology, ETH Zürich, Zürich, Switzerland.
Fabrice
F
Caudron
Institute of Biochemistry, Department of Biology, ETH Zürich, Zürich, Switzerland.
Annina
A
Denoth-Lippuner
Institute of Biochemistry, Department of Biology, ETH Zürich, Zürich, Switzerland.
Barbara
B
Boettcher
Institute of Biochemistry, Department of Biology, ETH Zürich, Zürich, Switzerland.
Stéphanie
S
Buvelot Frei
Department of Anatomy and Structural Biology, Albert Einstein College of Medicine of Yeshiva University, New York, United States.
Erik Lee
EL
Snapp
Institute of Biochemistry, Department of Biology, ETH Zürich, Zürich, Switzerland yves.barral@bc.biol.ethz.ch.
Yves
Y
Barral
D018797:Cell Cycle Proteins / Q000378:metabolism; D002455:Cell Division; D004058:Diffusion; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D059865:Endoplasmic Reticulum Stress; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism; D007425:Intracellular Membranes / Q000378:metabolism*; D008840:Microfilament Proteins / Q000378:metabolism; D009685:Nuclear Envelope / Q000378:metabolism; D010539:Permeability; D017510:Protein Folding; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D058112:Septins / Q000378:metabolism; D013107:Sphingolipids / Q000378:metabolism*; D013997:Time Factors; D020691:rab GTP-Binding Proteins / Q000378:metabolism
C091391:BUD5 protein, S cerevisiae; C107727:BUD6 protein, S cerevisiae; C073594:CDC24 protein, S cerevisiae; D018797:Cell Cycle Proteins; D020662:Guanine Nucleotide Exchange Factors; D008840:Microfilament Proteins; D029701:Saccharomyces cerevisiae Proteins; D013107:Sphingolipids; C084013:RSR1 protein, S cerevisiae; D058112:Septins; D020691:rab GTP-Binding Proteins
ER stress; aging; asymmetric cell division; diffusion barrier; sphingolipids