A screen for genes involved in respiration control and longevity in Schizosaccharomyces pombe.

We present results showing that glucose signaling has proaging effects in the yeast Schizosaccharomyces pombe. Deletion of the receptor that senses extracellular glucose (Git3) increases the life span of S. pombe, while constitutive activation of the Galpha subunit acting downstream of this receptor (Gpa2) shortens its life span.

The Schizosaccharomyces pombe Hsp104 disaggregase is unable to propagate the [PSI] prion.

The molecular chaperone Hsp104 is a crucial factor in the acquisition of thermotolerance in yeast. Under stress conditions, the disaggregase activity of Hsp104 facilitates the reactivation of misfolded proteins. Hsp104 is also involved in the propagation of fungal prions.

The epigenetic calnexin-independent state is induced in response to environmental changes.

Yeasts have evolved numerous responsive pathways to survive in fluctuating and stressful environments. The endoplasmic reticulum (ER) is sensitive to adverse conditions, which are detected by response pathways to ensure correct protein folding. Calnexin is an ER transmembrane chaperone acting in both quality control of folding and response to persistent stress.

Calnexin regulates apoptosis induced by inositol starvation in fission yeast.

Inositol is a precursor of numerous phospholipids and signalling molecules essential for the cell. Schizosaccharomyces pombe is naturally auxotroph for inositol as its genome does not have a homologue of the INO1 gene encoding inositol-1-phosphate synthase, the enzyme responsible for inositol biosynthesis. In this work, we demonstrate that inositol starvation in S.

A nucleolar protein allows viability in the absence of the essential ER-residing molecular chaperone calnexin.

In fission yeast, the ER-residing molecular chaperone calnexin is normally essential for viability. However, a specific mutant of calnexin that is devoid of chaperone function (Deltahcd_Cnx1p) induces an epigenetic state that allows growth of Schizosaccharomyces pombe without calnexin. This calnexin-independent (Cin) state was previously shown to be mediated via a non-chromosomal element exhibiting some prion-like features.

Inter-species complementation of the translocon beta subunit requires only its transmembrane domain.

In eukaryotes, proteins enter the secretory pathway through the translocon pore of the endoplasmic reticulum. This protein translocation channel is composed of three major subunits, called Sec61alpha, beta and gamma in mammals. Unlike the other subunits, the beta subunit is dispensable for translocation and cell viability in all organisms studied.

Calnexin is involved in apoptosis induced by endoplasmic reticulum stress in the fission yeast.

Stress conditions affecting the functions of the endoplasmic reticulum (ER) cause the accumulation of unfolded proteins. ER stress is counteracted by the unfolded-protein response (UPR). However, under prolonged stress the UPR initiates a proapoptotic response.

The calnexin-independent state does not compensate for all calnexin functions in Schizosaccharomyces pombe.

In the yeast Schizosaccharomyces pombe, the molecular chaperone calnexin (Cnx1p) has been shown to be essential for viability. However, we recently reported that, under certain circumstances, S. pombe cells are able to survive in the absence of calnexin/Cnx1p, indicating that an inducible pathway can complement the calnexin/Cnx1p essential function(s).

The 160 N-terminal residues of calnexin define a novel region supporting viability in Schizosaccharomyces pombe.

Protein secretion is a complex process that can be modulated by folding factors in the endoplasmic reticulum (ER), such as calnexin, a highly-conserved molecular chaperone involved in quality control. In Schizosaccharomyces pombe, calnexin (Cnx1p) is essential for cell viability. The calnexin/Cnx1p determinants required for viability have been mapped within the last 123 residues of its C-terminus.

Regulation of chronological aging in Schizosaccharomyces pombe by the protein kinases Pka1 and Sck2.

Budding yeast shows a progressive decline in viability after entering stationary phase, a phenomenon known as chronological aging. We show here that the fission yeast Schizosaccharomyces pombe also undergoes chronological aging and that the process is regulated by genes controlling two related nutrient signalling pathways. The first pathway includes the serine/threonine cAMP-activated protein kinase Pka1 and the second pathway comprises the serine/threonine kinase Sck2, a homologue of Saccharomyces cerevisiae SCH9.

Cell viability and secretion of active proteins in Schizosaccharomyces pombe do not require the chaperone function of calnexin.

Folding of newly synthesized proteins within the ER (endoplasmic reticulum) is a rate-limiting step in protein secretion. Thus ER molecular chaperones and foldases have a major impact in determining the rate and yield of these crucial cellular processes. Calnexin is a key ER chaperone implicated in the folding, retention and targeting for degradation of proteins that go through the secretory pathway.

A non-chromosomal factor allows viability of Schizosaccharomyces pombe lacking the essential chaperone calnexin.

Calnexin is a molecular chaperone playing key roles in protein folding and the quality control of this process in the endoplasmic reticulum. We, and others, have previously demonstrated that cnx1(+), the gene encoding the calnexin homologue in Schizosaccharomyces pombe, is essential for viability. We show that a particular cnx1 mutant induces a novel mechanism allowing the survival of S.

ROP-1, an RNA quality-control pathway component, affects Caenorhabditis elegans dauer formation.

Caenorhabditis elegans dauer formation is an alternative larval developmental pathway that the worm can take when environmental conditions become detrimental. Animals can survive several months in this stress-resistant stage and can resume normal development when growth conditions improve. Although the worms integrate a variety of sensory information to commit to dauer formation, it is currently unknown whether they also monitor internal cellular damage.

Although calnexin is essential in S. pombe, its highly conserved central domain is dispensable for viability.

In mammalian cells, the calnexin/calreticulin chaperones play a key role in glycoprotein folding and its control within the endoplasmic reticulum (ER), by interacting with folding intermediates via their monoglucosylated glycans. This lectin activity has been mapped in mammalian calnexin/calreticulin chaperones to the central region, which is a highly conserved feature of calnexin/calreticulin molecules across species. The central domain has also been implicated in Ca(2+) binding, and it has been proposed to be involved in the regulation of calcium homeostasis in the ER.

Assessing the function of the Ro ribonucleoprotein complex using Caenorhabditis elegans as a biological tool.

The Ro ribonucleoprotein complex (Ro RNP) was initially described as an autoimmune target in human diseases such as systemic lupus erythematosus and Sjögren's syndrome. In Xenopus and human cells, its general structure is composed of one major protein of 60 kDa, Ro60, that binds to one of four small RNA molecules, designated Y RNAs. Although no function has been assigned to the Ro RNP, Ro60 has been shown to bind mutant 5S ribosomal RNA (rRNA) molecules in Xenopus oocytes, suggesting a role for Ro60 in 5S rRNA biogenesis.

Interaction of mammalian neprilysin with binding protein and calnexin in Schizosaccharomyces pombe.

Neutral endopeptidase (neprilysin or NEP, EC 3.4.24.

The levels of the RoRNP-associated Y RNA are dependent upon the presence of ROP-1, the Caenorhabditis elegans Ro60 protein.

The Ro ribonucleoproteins (RoRNP) consist of at least one major protein of 60 kD, Ro60, and one small associated RNA, designated Y RNA. Although RoRNP have been found in all vertebrate species examined so far, their function remains unknown. The Caenorhabditis elegans rop-1 gene previously has been identified as encoding a Ro60 homologue.

Calnexin and BiP interact with acid phosphatase independently of glucose trimming and reglucosylation in Schizosaccharomyces pombe.

The association of newly synthesized glycoproteins with the ER molecular chaperones calnexin and immunoglobulin binding protein (BiP) has been well documented in a variety of higher eukaryotes. Here we report that Cnx1p, the calnexin homologue in Schizosaccharomyces pombe, associates with newly synthesized molecules of the secreted glycoprotein acid phosphatase. Unlike ligand binding to mammalian calnexin, glucose trimming and reglucosylation of acid phosphatase by UDP-Glc:glycoprotein glucosyltransferase were shown to be dispensable for its binding to Cnx1p.

A Schizosaccharomyces pombe gene encoding a novel polypeptide with a predicted alpha-helical rod structure found in the myosin and intermediate-filament families of proteins.

We have identified a Schizosaccharomyces pombe gene encoding a 461 amino acid polypeptide containing a predicted alpha-helical rod domain found in filamentous proteins. This gene, here designated noc1, is located immediately upstream from cnx1, the gene encoding the S. pombe homologue of mammalian calnexin, an endoplasmic reticulum chaperone [M.

A new stress protein: synthesis of Schizosaccharomyces pombe UDP--Glc:glycoprotein glucosyltransferase mRNA is induced by stress conditions but the enzyme is not essential for cell viability.

We have identified and begun the characterization of the gene encoding UDP-Glc:glycoprotein glucosyltransferase in Schizosaccharomyces pombe. This gene, here designated gpt1, codes for a polypeptide having a signal peptide of 18 amino acids followed by 1429 amino acids with no transmembrane domain, as expected for a soluble protein of the endoplasmic reticulum (ER). The C-terminal tetrapeptide PDEL most probably corresponds to a novel ER retention signal in this fission yeast.

The Caenorhabditis elegans rop-1 gene encodes the homologue of the human 60-kDa Ro autoantigen.

As a first step toward establishing a genetic system for the elucidation of the cellular role(s) of the Ro ribonucleoproteins (RoRNP), we have cloned the gene encoding the homologue of the human 60-kDa Ro protein (Ro60) in Caenorhabditis elegans (Ce). This Ce gene is present as a single copy and contains a 643-codon open reading frame interrupted by three introns. The encoded protein, Rop1p, shares 40% identity and 63% overall similarity with both the human and amphibian Ro60.