scholarly journals A sphingolipid-dependent diffusion barrier confines ER stress to the yeast mother cell

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Lori Clay ◽  
Fabrice Caudron ◽  
Annina Denoth-Lippuner ◽  
Barbara Boettcher ◽  
Stéphanie Buvelot Frei ◽  
...  
Keyword(s):  
Er Stress ◽  
Diffusion Barrier ◽  
Mother Cell ◽  
Budding Yeast ◽  
Lateral Diffusion ◽  
Physical Nature ◽  
Diffusion Barriers ◽  
Yeast Cells ◽  
Misfolded Proteins ◽  
Dependent Manner

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.

scholarly journals Septin-dependent compartmentalization of the endoplasmic reticulum during yeast polarized growth

2005 ◽  
Vol 169 (6) ◽  
pp. 897-908 ◽  
Author(s):  
Cosima Luedeke ◽  
Stéphanie Buvelot Frei ◽  
Ivo Sbalzarini ◽  
Heinz Schwarz ◽  
Anne Spang ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Plasma Membrane ◽  
Membrane Proteins ◽  
Diffusion Barriers ◽  
Yeast Cells ◽  
Dependent Manner ◽  
Protein Diffusion ◽  
Ultrastructural Studies ◽  
Bud Neck ◽  
Er Membrane

Polarized cells frequently use diffusion barriers to separate plasma membrane domains. It is unknown whether diffusion barriers also compartmentalize intracellular organelles. We used photobleaching techniques to characterize protein diffusion in the yeast endoplasmic reticulum (ER). Although a soluble protein diffused rapidly throughout the ER lumen, diffusion of ER membrane proteins was restricted at the bud neck. Ultrastructural studies and fluorescence microscopy revealed the presence of a ring of smooth ER at the bud neck. This ER domain and the restriction of diffusion for ER membrane proteins through the bud neck depended on septin function. The membrane-associated protein Bud6 localized to the bud neck in a septin-dependent manner and was required to restrict the diffusion of ER membrane proteins. Our results indicate that Bud6 acts downstream of septins to assemble a fence in the ER membrane at the bud neck. Thus, in polarized yeast cells, diffusion barriers compartmentalize the ER and the plasma membrane along parallel lines.

scholarly journals Mapping bilayer thickness in the ER membrane

2020 ◽  
Vol 6 (46) ◽  
pp. eaba5130 ◽  
Author(s):  
Rupali Prasad ◽  
Andrzej Sliwa-Gonzalez ◽  
Yves Barral
Keyword(s):  
Cleavage Plane ◽  
Lateral Diffusion ◽  
Physical Nature ◽  
Diffusion Barriers ◽  
Bilayer Thickness ◽  
Synthetic Membranes ◽  
Fluorescent Reporters ◽  
Discrete Domains ◽  
Lateral Organization ◽  
Er Membrane

In the plasma membrane and in synthetic membranes, resident lipids may laterally unmix to form domains of distinct biophysical properties. Whether lipids also drive the lateral organization of intracellular membranes is largely unknown. Here, we describe genetically encoded fluorescent reporters visualizing local variations in bilayer thickness. Using them, we demonstrate that long-chained ceramides promote the formation of discrete domains of increased bilayer thickness in the yeast ER, particularly in the future plane of cleavage and at ER–trans-Golgi contact sites. Thickening of the ER membrane in the cleavage plane contributed to the formation of lateral diffusion barriers, which restricted the passage of short, but not long, protein transmembrane domains between the mother and bud ER compartments. Together, our data establish that the ER membrane is laterally organized and that ceramides drive this process, and provide insights into the physical nature and biophysical mechanisms of the lateral diffusion barriers that compartmentalize the ER.

scholarly journals Heat stress promotes longevity in budding yeast by relaxing the confinement of age-promoting factors in the mother cell

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Sandro Baldi ◽  
Alessio Bolognesi ◽  
Anne Cornelis Meinema ◽  
Yves Barral
Keyword(s):  
Heat Stress ◽  
Stress Response ◽  
Nuclear Envelope ◽  
Diffusion Barrier ◽  
Barrier Function ◽  
Mother Cell ◽  
Yeast Cells ◽  
Daughter Cells ◽  
Higher Temperature ◽  
Aging Factors

Although individuals of many species inexorably age, a number of observations established that the rate of aging is modulated in response to a variety of mild stresses. Here, we investigated how heat stress promotes longevity in yeast. We show that upon growth at higher temperature, yeast cells relax the retention of DNA circles, which act as aging factors in the mother cell. The enhanced frequency at which circles redistribute to daughter cells was not due to changes of anaphase duration or nuclear shape but solely to the downregulation of the diffusion barrier in the nuclear envelope. This effect depended on the PKA and Tor1 pathways, downstream of stress-response kinase Pkc1. Inhibition of these responses restored barrier function and circle retention and abrogated the effect of heat stress on longevity. Our data indicate that redistribution of aging factors from aged cells to their progeny can be a mechanism for modulating longevity.

scholarly journals Glucocorticoids alleviate intestinal ER stress by enhancing protein folding and degradation of misfolded proteins

2013 ◽  
Vol 210 (6) ◽  
pp. 1201-1216 ◽  
Author(s):  
Indrajit Das ◽  
Chin Wen Png ◽  
Iulia Oancea ◽  
Sumaira Z. Hasnain ◽  
Rohan Lourie ◽  
...  
Keyword(s):  
Protein Folding ◽  
Glucocorticoid Receptor ◽  
Er Stress ◽  
Misfolded Proteins ◽  
Secretory Cells ◽  
Dependent Manner ◽  
Unfolded Protein ◽  
Genes Encoding ◽  
Glycosylation Inhibitor ◽  
The Unfolded Protein Response

Endoplasmic reticulum (ER) stress in intestinal secretory cells has been linked with colitis in mice and inflammatory bowel disease (IBD). Endogenous intestinal glucocorticoids are important for homeostasis and glucocorticoid drugs are efficacious in IBD. In Winnie mice with intestinal ER stress caused by misfolding of the Muc2 mucin, the glucocorticoid dexamethasone (DEX) suppressed ER stress and activation of the unfolded protein response (UPR), substantially restoring goblet cell Muc2 production. In mice lacking inflammation, a glucocorticoid receptor antagonist increased ER stress, and DEX suppressed ER stress induced by the N-glycosylation inhibitor, tunicamycin (Tm). In cultured human intestinal secretory cells, in a glucocorticoid receptor-dependent manner, DEX suppressed ER stress and UPR activation induced by blocking N-glycosylation, reducing ER Ca2+ or depleting glucose. DEX up-regulated genes encoding chaperones and elements of ER-associated degradation (ERAD), including EDEM1. Silencing EDEM1 partially inhibited DEX’s suppression of misfolding-induced ER stress, showing that DEX enhances ERAD. DEX inhibited Tm-induced MUC2 precursor accumulation, promoted production of mature mucin, and restored ER exit and secretion of Winnie mutant recombinant Muc2 domains, consistent with enhanced protein folding. In IBD, glucocorticoids are likely to ameliorate ER stress by promoting correct folding of secreted proteins and enhancing removal of misfolded proteins from the ER.

scholarly journals Nuclear envelope morphology constrains diffusion and promotes asymmetric protein segregation in closed mitosis

2012 ◽  
Vol 197 (7) ◽  
pp. 921-937 ◽  
Author(s):  
Barbara Boettcher ◽  
Tatiana T. Marquez-Lago ◽  
Mathias Bayer ◽  
Eric L. Weiss ◽  
Yves Barral
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Transcription Factor ◽  
Vegetative Growth ◽  
In Silico ◽  
Mother Cell ◽  
Daughter Cell ◽  
Diffusion Barriers ◽  
Yeast Cells ◽  
Nuclear Membranes ◽  
In Silico Modeling

During vegetative growth, Saccharomyces cerevisiae cells divide asymmetrically: the mother cell buds to produce a smaller daughter cell. This daughter asymmetrically inherits the transcription factor Ace2, which activates daughter-specific transcriptional programs. In this paper, we investigate when and how this asymmetry is established and maintained. We show that Ace2 asymmetry is initiated in the elongated, but undivided, anaphase nucleus. At this stage, the nucleoplasm was highly compartmentalized; little exchange was observed for nucleoplasmic proteins between mother and bud. Using photobleaching and in silico modeling, we show that diffusion barriers compartmentalize the nuclear membranes. In contrast, the behavior of proteins in the nucleoplasm is well explained by the dumbbell shape of the anaphase nucleus. This compartmentalization of the nucleoplasm promoted Ace2 asymmetry in anaphase nuclei. Thus, our data indicate that yeast cells use the process of closed mitosis and the morphological constraints associated with it to asymmetrically segregate nucleoplasmic components.

ER stress and toxic soluble misfolded proteins are present in diabetes and diabetic ketoacidosis in a sex dependent-manner

2021 ◽  
Author(s):  
Janara Furtado ◽  
Nicole R. Bearss ◽  
Cameron G Mccarthy ◽  
Munier Nazzal ◽  
William B. Hoffman ◽  
...  
Keyword(s):  
Er Stress ◽  
Diabetic Ketoacidosis ◽  
Misfolded Proteins ◽  
Dependent Manner

THE INTEGRITY OF THE CELL WALL DURING BUD FORMATION IN YEASTS

1965 ◽  
Vol 11 (3) ◽  
pp. 447-452 ◽  
Author(s):  
Dan O. McClary ◽  
Wilbert D. Bowers Jr.
Keyword(s):  
Cell Wall ◽  
Mother Cell ◽  
Budding Yeast ◽  
Dark Field ◽  
Yeast Cells ◽  
Constant Thickness ◽  
Full Thickness ◽  
Electron Microscopic ◽  
Bud Formation ◽  
Microscopic Studies

Dark-field and electron microscopic studies of budding yeast cells have shown an extension of a wall of full thickness, rather than a break in the wall, when the bud emerges. The bud appears as a minute bulge and grows steadily, not explosively, during which time both it and the mother cell are enclosed within a single wall. The wall maintains essentially a constant thickness throughout the growth of the bud, and at maturity both the wall and the cytoplasm of the two cells are separated by a cleavage wall which is laid down between them.

scholarly journals Author response: A sphingolipid-dependent diffusion barrier confines ER stress to the yeast mother cell

2014 ◽  
Author(s):  
Lori Clay ◽  
Fabrice Caudron ◽  
Annina Denoth-Lippuner ◽  
Barbara Boettcher ◽  
Stéphanie Buvelot Frei ◽  
...  
Keyword(s):  
Er Stress ◽  
Diffusion Barrier ◽  
Mother Cell ◽  
Author Response
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