The Hsp70/90 cochaperone, Sti1, suppresses proteotoxicity by regulating spatial quality control of amyloid-like proteins.

Abstract:

:Conformational diseases are associated with the conversion of normal proteins into aggregation-prone toxic conformers with structures similar to that of β-amyloid. Spatial distribution of amyloid-like proteins into intracellular quality control centers can be beneficial, but cellular mechanisms for protective aggregation remain unclear. We used a high-copy suppressor screen in yeast to identify roles for the Hsp70 system in spatial organization of toxic polyglutamine-expanded Huntingtin (Huntingtin with 103Q glutamine stretch [Htt103Q]) into benign assemblies. Under toxic conditions, Htt103Q accumulates in unassembled states and speckled cytosolic foci. Subtle modulation of Sti1 activity reciprocally affects Htt toxicity and the packaging of Htt103Q into foci. Loss of Sti1 exacerbates Htt toxicity and hinders foci formation, whereas elevation of Sti1 suppresses Htt toxicity while organizing small Htt103Q foci into larger assemblies. Sti1 also suppresses cytotoxicity of the glutamine-rich yeast prion [RNQ+] while reorganizing speckled Rnq1-monomeric red fluorescent protein into distinct foci. Sti1-inducible foci are perinuclear and contain proteins that are bound by the amyloid indicator dye thioflavin-T. Sti1 is an Hsp70 cochaperone that regulates the spatial organization of amyloid-like proteins in the cytosol and thereby buffers proteotoxicity caused by amyloid-like proteins.

journal_name

Mol Biol Cell

authors

Wolfe KJ,Ren HY,Trepte P,Cyr DM

doi

10.1091/mbc.E13-06-0315

subject

Has Abstract

pub_date

2013-12-01 00:00:00

pages

3588-602

issue

23

eissn

1059-1524

issn

1939-4586

pii

mbc.E13-06-0315

journal_volume

24

pub_type

杂志文章
  • Two related kinesins, klp5+ and klp6+, foster microtubule disassembly and are required for meiosis in fission yeast.

    abstract::The kinesin superfamily of microtubule motor proteins is important in many cellular processes, including mitosis and meiosis, vesicle transport, and the establishment and maintenance of cell polarity. We have characterized two related kinesins in fission yeast, klp5+ and klp6+,, that are amino-terminal motors of the K...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.12.12.3919

    authors: West RR,Malmstrom T,Troxell CL,McIntosh JR

    更新日期:2001-12-01 00:00:00

  • Autoinhibition of Jak2 tyrosine kinase is dependent on specific regions in its pseudokinase domain.

    abstract::Jak tyrosine kinases have a unique domain structure containing a kinase domain (JH1) adjacent to a catalytically inactive pseudokinase domain (JH2). JH2 is crucial for inhibition of basal Jak activity, but the mechanism of this regulation has remained elusive. We show that JH2 negatively regulated Jak2 in bacterial ce...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e02-06-0342

    authors: Saharinen P,Vihinen M,Silvennoinen O

    更新日期:2003-04-01 00:00:00

  • The Pif1 family in prokaryotes: what are our helicases doing in your bacteria?

    abstract::Pif1 family helicases, which are found in nearly all eukaryotes, have important roles in both nuclear and mitochondrial genome maintenance. Recently, the increasing availability of genome sequences has revealed that Pif1 helicases are also widely found in diverse prokaryotes, but it is currently unknown what physiolog...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E11-01-0045

    authors: Bochman ML,Judge CP,Zakian VA

    更新日期:2011-06-15 00:00:00

  • Actomyosin sliding is attenuated in contractile biomimetic cortices.

    abstract::Myosin II motors embedded within the actin cortex generate contractile forces to modulate cell shape in essential behaviors, including polarization, migration, and division. In sarcomeres, myosin II-mediated sliding of antiparallel F-actin is tightly coupled to myofibril contraction. By contrast, cortical F-actin is h...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E13-08-0450

    authors: Murrell M,Gardel ML

    更新日期:2014-06-15 00:00:00

  • Genetic analysis of lysosomal trafficking in Caenorhabditis elegans.

    abstract::The intestinal cells of Caenorhabditis elegans embryos contain prominent, birefringent gut granules that we show are lysosome-related organelles. Gut granules are labeled by lysosomal markers, and their formation is disrupted in embryos depleted of AP-3 subunits, VPS-16, and VPS-41. We define a class of gut granule lo...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e05-01-0060

    authors: Hermann GJ,Schroeder LK,Hieb CA,Kershner AM,Rabbitts BM,Fonarev P,Grant BD,Priess JR

    更新日期:2005-07-01 00:00:00

  • Temperature-modulated alternative splicing and promoter use in the Circadian clock gene frequency.

    abstract::The expression of FREQUENCY, a central component of the circadian clock in Neurospora crassa, shows daily cycles that are exquisitely sensitive to the environment. Two forms of FRQ that differ in length by 99 amino acids, LFRQ and SFRQ, are synthesized from alternative initiation codons and the change in their ratio a...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e05-08-0756

    authors: Colot HV,Loros JJ,Dunlap JC

    更新日期:2005-12-01 00:00:00

  • Transforming growth factor-beta1 mediates epithelial to mesenchymal transdifferentiation through a RhoA-dependent mechanism.

    abstract::Transforming growth factor-beta1 (TGF-beta) can be tumor suppressive, but it can also enhance tumor progression by stimulating the complex process of epithelial-to-mesenchymal transdifferentiaion (EMT). The signaling pathway(s) that regulate EMT in response to TGF-beta are not well understood. We demonstrate the acqui...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.12.1.27

    authors: Bhowmick NA,Ghiassi M,Bakin A,Aakre M,Lundquist CA,Engel ME,Arteaga CL,Moses HL

    更新日期:2001-01-01 00:00:00

  • The nfkb1 promoter is controlled by proteins of the Ets family.

    abstract::The gene encoding NFKB1 is autoregulated, responding to NF-kappa B/Rel activation through NF-kappa B binding sites in its promoter, which also contains putative sites for Ets proteins. One of the Ets sites, which we refer to as EBS4, is located next to an NF-kappa B/Rel binding site, kB3, which is absolutely required ...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.8.2.313

    authors: Lambert PF,Ludford-Menting MJ,Deacon NJ,Kola I,Doherty RR

    更新日期:1997-02-01 00:00:00

  • RNA polymerase III in Cajal bodies and lampbrush chromosomes of the Xenopus oocyte nucleus.

    abstract::We used immunofluorescence to study the distribution and targeting of RNA polymerase (pol) III subunits and pol III transcription factors in the Xenopus laevis oocyte nucleus. Antibodies against several of these proteins stained Cajal bodies and approximately 90 specific sites on the lampbrush chromosomes. Some of the...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e02-05-0281

    authors: Murphy C,Wang Z,Roeder RG,Gall JG

    更新日期:2002-10-01 00:00:00

  • Human adenine nucleotide translocases physically and functionally interact with respirasomes.

    abstract::Members of the adenine nucleotide translocase (ANT) family exchange ADP for ATP across the mitochondrial inner membrane, an activity that is essential for oxidative phosphorylation (OXPHOS). Mutations in or dysregulation of ANTs is associated with progressive external ophthalmoplegia, cardiomyopathy, nonsyndromic inte...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E17-03-0195

    authors: Lu YW,Acoba MG,Selvaraju K,Huang TC,Nirujogi RS,Sathe G,Pandey A,Claypool SM

    更新日期:2017-06-01 00:00:00

  • Half a century of "the nuclear matrix".

    abstract::A cell fraction that would today be termed "the nuclear matrix" was first described and patented in 1948 by Russian investigators. In 1974 this fraction was rediscovered and promoted as a fundamental organizing principle of eukaryotic gene expression. Yet, convincing evidence for this functional role of the nuclear ma...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章,评审

    doi:10.1091/mbc.11.3.799

    authors: Pederson T

    更新日期:2000-03-01 00:00:00

  • JAMP optimizes ERAD to protect cells from unfolded proteins.

    abstract::Clearance of misfolded proteins from the ER is central for maintenance of cellular homeostasis. This process requires coordinated recognition, ER-cytosol translocation, and finally ubiquitination-dependent proteasomal degradation. Here, we identify an ER resident seven-transmembrane protein (JAMP) that links ER chaper...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e08-08-0839

    authors: Tcherpakov M,Broday L,Delaunay A,Kadoya T,Khurana A,Erdjument-Bromage H,Tempst P,Qiu XB,DeMartino GN,Ronai Z

    更新日期:2008-11-01 00:00:00

  • Regulation of macropinocytosis by p21-activated kinase-1.

    abstract::The process of macropinocytosis is an essential aspect of normal cell function, contributing to both growth and motile processes of cells. p21-activated kinases (PAKs) are targets for activated Rac and Cdc42 guanosine 5'-triphosphatases and have been shown to regulate the actin-myosin cytoskeleton. In fibroblasts PAK1...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.11.10.3341

    authors: Dharmawardhane S,Schürmann A,Sells MA,Chernoff J,Schmid SL,Bokoch GM

    更新日期:2000-10-01 00:00:00

  • The GTPase SPAG-1 orchestrates meiotic program by dictating meiotic resumption and cytoskeleton architecture in mouse oocytes.

    abstract::In mammals, a finite population of oocytes is generated during embryogenesis, and proper oocyte meiotic divisions are crucial for fertility. Sperm-associated antigen 1 (SPAG-1) has been implicated in infertility and tumorigenesis; however, its relevance in cell cycle programs remains rudimentary. Here we explore a nov...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E16-02-0132

    authors: Huang C,Wu D,Khan FA,Jiao X,Guan K,Huo L

    更新日期:2016-06-01 00:00:00

  • Mammalian late vacuole protein sorting orthologues participate in early endosomal fusion and interact with the cytoskeleton.

    abstract::In Saccharomyces cerevisiae, the class C vacuole protein sorting (Vps) proteins, together with Vam2p/Vps41p and Vam6p/Vps39p, form a complex that interacts with soluble N-ethylmaleimide-sensitive factor attachment protein receptor and Rab proteins to "tether" vacuolar membranes before fusion. To determine a role for t...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e03-06-0358

    authors: Richardson SC,Winistorfer SC,Poupon V,Luzio JP,Piper RC

    更新日期:2004-03-01 00:00:00

  • Epsilon-tubulin is an essential component of the centriole.

    abstract::Centrioles and basal bodies are cylinders composed of nine triplet microtubule blades that play essential roles in the centrosome and in flagellar assembly. Chlamydomonas cells with the bld2-1 mutation fail to assemble doublet and triplet microtubules and have defects in cleavage furrow placement and meiosis. Using po...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e02-04-0205

    authors: Dutcher SK,Morrissette NS,Preble AM,Rackley C,Stanga J

    更新日期:2002-11-01 00:00:00

  • The secretory pathway at 50: a golden anniversary for some momentous grains of silver.

    abstract::The secretory pathway along which newly synthesized secretory and membrane proteins traffic through the cell was revealed in two articles published 50 years ago. This discovery was the culmination of decades of effort to unite the power of biochemical and morphological methodologies in order to elucidate the dynamic n...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E16-07-0508

    authors: Matlin KS,Caplan MJ

    更新日期:2017-01-15 00:00:00

  • An elaborate classification of SNARE proteins sheds light on the conservation of the eukaryotic endomembrane system.

    abstract::Proteins of the SNARE (soluble N-ethylmalemide-sensitive factor attachment protein receptor) family are essential for the fusion of transport vesicles with an acceptor membrane. Despite considerable sequence divergence, their mechanism of action is conserved: heterologous sets assemble into membrane-bridging SNARE com...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e07-03-0193

    authors: Kloepper TH,Kienle CN,Fasshauer D

    更新日期:2007-09-01 00:00:00

  • Angiomotin links ROCK and YAP signaling in mechanosensitive differentiation of neural stem cells.

    abstract::Mechanical cues regulate the function of a broad range of stem cells in culture and in tissue. For example, soft substrates promote the neuronal differentiation of neural stem cells (NSCs) by suppressing cytoskeletal contractility. However, the mechanisms that link cytoskeletal signaling to the transcriptional regulat...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E19-11-0602

    authors: Kang PH,Schaffer DV,Kumar S

    更新日期:2020-03-01 00:00:00

  • Identification of the nuclear localization signal in Xenopus cyclin E and analysis of its role in replication and mitosis.

    abstract::Cyclin-dependent kinase (Cdk)2/cyclin E is imported into nuclei assembled in Xenopus egg extracts by a pathway that requires importin-alpha and -beta. Here, we identify a basic nuclear localization sequence (NLS) in the N-terminus of Xenopus cyclin E. Mutation of the NLS eliminated nuclear accumulation of both cyclin ...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e02-07-0449

    authors: Moore JD,Kornbluth S,Hunt T

    更新日期:2002-12-01 00:00:00

  • Developmental expression of spectrins in rat skeletal muscle.

    abstract::Skeletal muscle contains spectrin (or spectrin I) and fodrin (or spectrin II), members of the spectrin supergene family. We used isoform-specific antibodies and cDNA probes to investigate the molecular forms, developmental expression, and subcellular localization of the spectrins in skeletal muscle of the rat. We repo...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.9.1.47

    authors: Zhou D,Ursitti JA,Bloch RJ

    更新日期:1998-01-01 00:00:00

  • Cell cycle-dependent recruitment of telomerase RNA and Cajal bodies to human telomeres.

    abstract::Telomerase is a ribonucleoprotein enzyme that counteracts replicative telomere erosion by adding telomeric sequence repeats onto chromosome ends. Despite its well-established role in telomere synthesis, telomerase has not yet been detected at telomeres. The RNA component of human telomerase (hTR) resides in the nucleo...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e05-09-0904

    authors: Jády BE,Richard P,Bertrand E,Kiss T

    更新日期:2006-02-01 00:00:00

  • Ancient complement and lineage-specific evolution of the Sec7 ARF GEF proteins in eukaryotes.

    abstract::Guanine nucleotide exchange factors (GEFs) are the initiators of signaling by every regulatory GTPase, which in turn act to regulate a wide array of essential cellular processes. To date, each family of GTPases is activated by distinct families of GEFs. Bidirectional membrane trafficking is regulated by ADP-ribosylati...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E19-01-0073

    authors: Pipaliya SV,Schlacht A,Klinger CM,Kahn RA,Dacks J

    更新日期:2019-07-15 00:00:00

  • Src-dependent TrkA transactivation is required for pituitary adenylate cyclase-activating polypeptide 38-mediated Rit activation and neuronal differentiation.

    abstract::Pituitary adenylate cyclase-activating polypeptide (PACAP) is a potent neuropeptide that possesses both neurotrophic and neurodevelopmental effects. Recently, the Rit GTPase was found to be activated by a novel Galpha/cAMP/exchange protein activated by cyclic AMP (Epac)-dependent signaling pathway and required for PAC...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e09-12-1033

    authors: Shi GX,Jin L,Andres DA

    更新日期:2010-05-01 00:00:00

  • Fission yeast minichromosome loss mutants mis cause lethal aneuploidy and replication abnormality.

    abstract::Precise chromosome transmission in cell division cycle is maintained by a number of genes. The attempt made in the present study was to isolate temperature-sensitive (ts) fission yeast mutants that display high loss rates of minichromosomes at permissive or semipermissive temperature (designated mis). By colony color ...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.5.10.1145

    authors: Takahashi K,Yamada H,Yanagida M

    更新日期:1994-10-01 00:00:00

  • In vitro BioID: mapping the CENP-A microenvironment with high temporal and spatial resolution.

    abstract::The centromere is located at the primary constriction of condensed chromosomes where it acts as a platform regulating chromosome segregation. The histone H3 variant CENP-A is the foundation for kinetochore formation. CENP-A directs the formation of a highly dynamic molecular neighborhood whose temporal characterizatio...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E18-12-0799

    authors: Remnant L,Booth DG,Vargiu G,Spanos C,Kerr ARW,Earnshaw WC

    更新日期:2019-05-15 00:00:00

  • Myo1c binds phosphoinositides through a putative pleckstrin homology domain.

    abstract::Myo1c is a member of the myosin superfamily that binds phosphatidylinositol-4,5-bisphosphate (PIP(2)), links the actin cytoskeleton to cellular membranes and plays roles in mechano-signal transduction and membrane trafficking. We located and characterized two distinct membrane binding sites within the regulatory and t...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e06-05-0449

    authors: Hokanson DE,Laakso JM,Lin T,Sept D,Ostap EM

    更新日期:2006-11-01 00:00:00

  • Actin cross-linking proteins cortexillin I and II are required for cAMP signaling during Dictyostelium chemotaxis and development.

    abstract::Starvation induces Dictyostelium amoebae to secrete cAMP, toward which other amoebae stream, forming multicellular mounds that differentiate and develop into fruiting bodies containing spores. We find that the double deletion of cortexillin (ctx) I and II alters the actin cytoskeleton and substantially inhibits all mo...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.E11-09-0764

    authors: Shu S,Liu X,Kriebel PW,Daniels MP,Korn ED

    更新日期:2012-01-01 00:00:00

  • Slx1-Slx4 are subunits of a structure-specific endonuclease that maintains ribosomal DNA in fission yeast.

    abstract::In most eukaryotes, genes encoding ribosomal RNAs (rDNA) are clustered in long tandem head-to-tail repeats. Studies of Saccharomyces cerevisiae have indicated that rDNA copy number is maintained through recombination events associated with site-specific blockage of replication forks (RFs). Here, we describe two Schizo...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.e03-08-0586

    authors: Coulon S,Gaillard PHL,Chahwan C,McDonald WH,Yates JR 3rd,Russell P

    更新日期:2004-01-01 00:00:00

  • Isolation of protein glycosylation mutants in the fission yeast Schizosaccharomyces pombe.

    abstract::We have isolated mutants in the fission yeast Schizosaccharomyces pombe that are defective in protein glycosylation. A collection of osmotically sensitive mutants was prepared and screened for glycosylation defects using lectin staining as an assay. Mutants singly defective in four glycoprotein synthesis genes (gps1-4...

    journal_title:Molecular biology of the cell

    pub_type: 杂志文章

    doi:10.1091/mbc.6.5.485

    authors: Huang KM,Snider MD

    更新日期:1995-05-01 00:00:00