scholarly journals The Unfolded Protein Response Pathway in the Yeast Kluyveromyces lactis. A Comparative View among Yeast Species

Cells ◽  
2018 ◽  
Vol 7 (8) ◽  
pp. 106 ◽  
Author(s):  
Mariana Hernández-Elvira ◽  
Francisco Torres-Quiroz ◽  
Abril Escamilla-Ayala ◽  
Eunice Domínguez-Martin ◽  
Ricardo Escalante ◽  
...  
Keyword(s):  
Unfolded Protein Response ◽  
Mammalian Cells ◽  
Yeast Species ◽  
Kluyveromyces Lactis ◽  
Protein Accumulation ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Protein Response ◽  
Er Homeostasis ◽  
Upr Pathway

Eukaryotic cells have evolved signalling pathways that allow adaptation to harmful conditions that disrupt endoplasmic reticulum (ER) homeostasis. When the function of the ER is compromised in a condition known as ER stress, the cell triggers the unfolded protein response (UPR) in order to restore ER homeostasis. Accumulation of misfolded proteins due to stress conditions activates the UPR pathway. In mammalian cells, the UPR is composed of three branches, each containing an ER sensor (PERK, ATF6 and IRE1). However, in yeast species, the only sensor present is the inositol-requiring enzyme Ire1. To cope with unfolded protein accumulation, Ire1 triggers either a transcriptional response mediated by a transcriptional factor that belongs to the bZIP transcription factor family or an mRNA degradation process. In this review, we address the current knowledge of the UPR pathway in several yeast species: Saccharomyces cerevisiae, Schizosaccharomyces pombe, Candida glabrata, Cryptococcus neoformans, and Candida albicans. We also include unpublished data on the UPR pathway of the budding yeast Kluyveromyces lactis. We describe the basic components of the UPR pathway along with similarities and differences in the UPR mechanism that are present in these yeast species.

scholarly journals Two Distinctly Localized P-Type ATPases Collaborate to Maintain Organelle Homeostasis Required for Glycoprotein Processing and Quality Control

2002 ◽  
Vol 13 (11) ◽  
pp. 3955-3966 ◽  
Author(s):  
Shilpa Vashist ◽  
Christian G. Frank ◽  
Claude A. Jakob ◽  
Davis T.W. Ng
Keyword(s):  
Quality Control ◽  
Unfolded Protein Response ◽  
Secretory Pathway ◽  
Ion Homeostasis ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Coa Reductase ◽  
Protein Response ◽  
P Type ◽  
Er Homeostasis

Membrane transporter proteins are essential for the maintenance of cellular ion homeostasis. In the secretory pathway, the P-type ATPase family of transporters is found in every compartment and the plasma membrane. Here, we report the identification of COD1/SPF1(control of HMG-CoA reductase degradation/SPF1) through genetic strategies intended to uncover genes involved in protein maturation and endoplasmic reticulum (ER)-associated degradation (ERAD), a quality control pathway that rids misfolded proteins. Cod1p is a putative ER P-type ATPase whose expression is regulated by the unfolded protein response, a stress-inducible pathway used to monitor and maintain ER homeostasis. COD1 mutants activate the unfolded protein response and are defective in a variety of functions apart from ERAD, which further support a homeostatic role.COD1 mutants display phenotypes similar to strains lacking Pmr1p, a Ca2+/Mn2+pump that resides in the medial-Golgi. Because of its localization, the previously reported role of PMR1 in ERAD was somewhat enigmatic. A clue to their respective roles came from observations that the two genes are not generally required for ERAD. We show that the specificity is rooted in a requirement for both genes in protein-linked oligosaccharide trimming, a requisite ER modification in the degradation of some misfolded glycoproteins. Furthermore, Cod1p, like Pmr1p, is also needed for the outer chain modification of carbohydrates in the Golgi apparatus despite its ER localization. In strains deleted of both genes, these activities are nearly abolished. The presence of either protein alone, however, can support partial function for both compartments. Taken together, our results reveal an interdependent relationship between two P-type ATPases to maintain homeostasis of the organelles where they reside.

scholarly journals Phosphorylation of Pal2 by the protein kinases Kin1 and Kin2 modulates HAC1 mRNA splicing in the unfolded protein response in yeast

2021 ◽  
Vol 14 (684) ◽  
pp. eaaz4401
Author(s):  
Chandrima Ghosh ◽  
Jagadeesh Kumar Uppala ◽  
Leena Sathe ◽  
Charlotte I. Hammond ◽  
Ashish Anshu ◽  
...  
Keyword(s):  
Unfolded Protein Response ◽  
Protein Kinases ◽  
Cellular Stress ◽  
Mrna Processing ◽  
Mrna Splicing ◽  
Cellular Stress Response ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Protein Response ◽  
Er Homeostasis

During cellular stress in the budding yeast Saccharomyces cerevisiae, an endoplasmic reticulum (ER)–resident dual kinase and RNase Ire1 splices an intron from HAC1 mRNA in the cytosol, thereby releasing its translational block. Hac1 protein then activates an adaptive cellular stress response called the unfolded protein response (UPR) that maintains ER homeostasis. The polarity-inducing protein kinases Kin1 and Kin2 contribute to HAC1 mRNA processing. Here, we showed that an RNA-protein complex that included the endocytic proteins Pal1 and Pal2 mediated HAC1 mRNA splicing downstream of Kin1 and Kin2. We found that Pal1 and Pal2 bound to the 3′ untranslated region (3′UTR) of HAC1 mRNA, and a yeast strain lacking both Pal1 and Pal2 was deficient in HAC1 mRNA processing. We also showed that Kin1 and Kin2 directly phosphorylated Pal2, and that a nonphosphorylatable Pal2 mutant could not rescue the UPR defect in a pal1Δ pal2Δ strain. Thus, our work uncovers a Kin1/2-Pal2 signaling pathway that coordinates HAC1 mRNA processing and ER homeostasis.

scholarly journals Dysregulation in the Unfolded Protein Response in the FGR Rat Pancreas

2020 ◽  
Vol 2020 ◽  
pp. 1-11 ◽  
Author(s):  
Xiaomei Liu ◽  
Yanyan Guo ◽  
Jun Wang ◽  
Liangliang Zhu ◽  
Linlin Gao
Keyword(s):  
Protein Kinase ◽  
Unfolded Protein Response ◽  
Binding Protein ◽  
Protein Kinase R ◽  
Pregnant Rats ◽  
Fetal Pancreas ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Protein Response ◽  
Upr Pathway

Accumulating evidence suggests that fetal growth restriction (FGR) leads to the development of diabetes mellitus in adults. The aim of this study was to investigate the effect of protein malnutrition in utero on the pancreatic unfolded protein response (UPR) pathway in FGR offspring. An FGR model was developed by feeding a low-protein diet to pregnant rats throughout gestation. Eighty-four UPR pathway components in the pancreas were investigated by quantitative PCR arrays and confirmed by qPCR and western blotting. Activating transcription factor (Atf4 and Atf6), herpud1, protein kinase R-like endoplasmic reticulum kinase (Perk), X-box binding protein 1 (Xbp1), and the phosphorylation of eIF2α were upregulated, while cyclic AMP-responsive element-binding protein 3-like protein was markedly downregulated in FGR fetuses compared with controls. Investigation in adult offspring revealed temporal changes, for most UPR factors restored to normal, except that dysregulation of Atf6 and Creb3l3 maintained until adulthood. Moreover, autophagy was suppressed in FGR fetal pancreas and may be associated with decreased activation of AMP-activated protein kinase (Ampk). Apoptosis regulators Bax and cleaved-caspase 3 and 9 were upregulated in FGR fetal pancreas. Given that islet size and number were decreased in FGR fetus, we speculated that the aberrant intrauterine milieu impaired UPR signaling in fetal pancreas development. Whether these alterations early in life contribute to the predisposition of FGR fetuses to adult metabolic disorders invites further exploration.

scholarly journals A novel role in cytokinesis reveals a housekeeping function for the unfolded protein response

2007 ◽  
Vol 177 (6) ◽  
pp. 1017-1027 ◽  
Author(s):  
Alicia A. Bicknell ◽  
Anna Babour ◽  
Christine M. Federovitch ◽  
Maho Niwa
Keyword(s):  
Cell Cycle ◽  
Unfolded Protein Response ◽  
Normal Cell ◽  
Growth Conditions ◽  
Unfolded Protein ◽  
Functional Capabilities ◽  
Cellular Events ◽  
The Unfolded Protein Response ◽  
Protein Response ◽  
Upr Pathway

The unfolded protein response (UPR) pathway helps cells cope with endoplasmic reticulum (ER) stress by activating genes that increase the ER's functional capabilities. We have identified a novel role for the UPR pathway in facilitating budding yeast cytokinesis. Although other cell cycle events are unaffected by conditions that disrupt ER function, cytokinesis is sensitive to these conditions. Moreover, efficient cytokinesis requires the UPR pathway even during unstressed growth conditions. UPR-deficient cells are defective in cytokinesis, and cytokinesis mutants activate the UPR. The UPR likely achieves its role in cytokinesis by sensing small changes in ER load and making according changes in ER capacity. We propose that cytokinesis is one of many cellular events that require a subtle increase in ER function and that the UPR pathway has a previously uncharacterized housekeeping role in maintaining ER plasticity during normal cell growth.

scholarly journals Protein Serine/Threonine Phosphatase Ptc2p Negatively Regulates the Unfolded-Protein Response by Dephosphorylating Ire1p Kinase

1998 ◽  
Vol 18 (4) ◽  
pp. 1967-1977 ◽  
Author(s):  
Ajith A. Welihinda ◽  
Witoon Tirasophon ◽  
Sarah R. Green ◽  
Randal J. Kaufman
Keyword(s):  
Unfolded Protein Response ◽  
Transmembrane Protein ◽  
Null Alleles ◽  
Dependent Manner ◽  
Unfolded Proteins ◽  
Interaction Domain ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Protein Response ◽  
Upr Pathway

ABSTRACT Cells respond to the accumulation of unfolded proteins in the endoplasmic reticulum (ER) by increasing the transcription of the genes encoding ER-resident chaperone proteins. Ire1p is a transmembrane protein kinase that transmits the signal from unfolded proteins in the lumen of the ER by a mechanism that requires oligomerization andtrans-autophosphorylation of its cytoplasmic-nucleoplasmic kinase domain. Activation of Ire1p induces a novel spliced form ofHAC1 mRNA that produces Hac1p, a transcription factor that is required for activation of the transcription of genes under the control of the unfolded-protein response (UPR) element. Searching for proteins that interact with Ire1p in Saccharomyces cerevisiae, we isolated PTC2, which encodes a serine/threonine phosphatase of type 2C. The Ptc2p interaction with Ire1p is specific, direct, dependent on Ire1p phosphorylation, and mediated through a kinase interaction domain within Ptc2p. Ptc2p dephosphorylates Ire1p efficiently in an Mg2+-dependent manner in vitro. PTC2 is nonessential for growth and negatively regulates the UPR pathway. Strains carrying null alleles ofPTC2 have a three- to fourfold-increased UPR and increased levels of spliced HAC1 mRNA. Overexpression of wild-type Ptc2p but not catalytically inactive Ptc2p reduces levels of splicedHAC1 mRNA and attenuates the UPR, demonstrating that the phosphatase activity of Ptc2p is required for regulation of the UPR. These results demonstrate that Ptc2p downregulates the UPR by dephosphorylating Ire1p and reveal a novel mechanism of regulation in the UPR pathway upstream of the HAC1 mRNA splicing event.

Slower rescue of ER homeostasis by the unfolded protein response pathway associated with common variable immunodeficiency

2008 ◽  
Vol 45 (10) ◽  
pp. 2990-2997 ◽  
Author(s):  
Juliana S. Kuribayashi ◽  
Cíntia R. Bombardieri ◽  
Gisele V. Baracho ◽  
Júlio Aliberti ◽  
Fabiana S. Machado ◽  
...  
Keyword(s):  
Unfolded Protein Response ◽  
Common Variable Immunodeficiency ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Protein Response ◽  
Er Homeostasis ◽  
Common Variable
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